Skip to main content

Advertisement

SpringerLink
Log in

Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response

  • Review
  • Published:
Cellular Oncology Aims and scope Submit manuscript

Abstract

Background

Cytotoxic chemotherapy improves survival for some, but not all, cancer patients. Non-responders may experience unnecessary toxicity and cancer progression, thus creating an urgent need for biomarkers that can predict the response to chemotherapy. So far, the search for such biomarkers has primarily been focused on the cancer cells and less on their surrounding stroma. This stroma is known to act as a key regulator of tumour progression and, in addition, has been associated with drug delivery and drug efficacy. Fibroblasts represent the major cell type in cancer-associated stroma and they secrete extracellular matrix proteins as well as growth factors. This Medline-based literature review summarises the results from studies on epithelial cancers and aimed at investigating relationships between the quantity and quality of the intra-tumoral stroma, the cancer-associated fibroblasts, the proteins they produce and the concomitant response to chemotherapy. Biomarkers were selected for review that are known to affect cancer-related characteristics and patient prognosis.

Results

The current literature supports the hypothesis that biomarkers derived from the tumour stroma may be useful to predict response to chemotherapy. This notion appears to be related to the overall quantity and cellularity of the intra-tumoural stroma and the predominant constituents of the extracellular matrix.

Conclusion

Increasing evidence is emerging showing that tumour-stroma interactions may not only affect tumour progression and patient prognosis, but also the response to chemotherapy. The tumour stroma-derived biomarkers that appear to be most appropriate to determine the patient’s response to chemotherapy vary by tumour origin and the availability of pre-treatment tissue. For patients scheduled for adjuvant chemotherapy, the most promising biomarker appears to be the PLAU: SERPINE complex, whereas for patients scheduled for neo-adjuvant chemotherapy the tumour stroma quantity appears to be most relevant.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

CAF:

cancer associated fibroblast

CMF:

cyclophosphamide methotrexate and 5-fluorouracil

CTGF:

connective tissue growth factor

ECM:

extracellular matrix

EFEMP1:

fibulin 3

ELISA:

enzyme linked immunosorbent assay

FBLN1:

fibulin 1

FN1:

fibronectin

HA:

hyaluronan

HGF:

hepatocyte growth factor

MMP:

matrix metalloproteinase

PTK:

protein tyrosine kinase

SCLC:

small cell lung cancer

SDC1:

syndecan 1

SERPINE1:

serine protease inhibitor type-1

SPARC:

secreted protein, acidic, cysteine-rich

TIMP1:

tissue inhibitor of metalloproteinase-1

PLAU:

urokinase-type plasminogen activator

References

  1. D. Hanahan, R.A. Weinberg, S. Francisco, The hallmarks of cancer. Cell. 100, 57–70 (2000)

    Article  PubMed  CAS  Google Scholar 

  2. G. Chong, D. Cunningham, Oesophageal cancer: preoperative chemotherapy. Ann. Oncol. 15(Suppl 4), iv87–iv91 (2004)

    Article  PubMed  Google Scholar 

  3. N. Tamura, T. Hasebe, N. Okada, T. Houjoh, S. Akashi-Tanaka, C. Shimizu, T. Shibata, Y. Sasajima, M. Iwasaki, T. Kinoshita, Tumor histology in lymph vessels and lymph nodes for the accurate prediction of outcome among breast cancer patients treated with neoadjuvant chemotherapy. Cancer Sci. 100, 1823–1833 (2009)

    Article  PubMed  CAS  Google Scholar 

  4. The Cochrane Collaboration: Advanced Bladder Cancer Meta-analysis Collaboration, Neoadjuvant chemotherapy for invasive bladder cancer (Review). The Cochrane Library. (2008).

  5. E. Kent, M. Hussain, Neoadjuvant Therapy for Prostate Cancer: An Oncologist’s Perspective. Rev Urol. 5(Suppl 3), S28–S37 (2003)

    PubMed  Google Scholar 

  6. T. Delaunoit, S.R. Alberts, D.J. Sargent, E. Green, R.M. Goldberg, J. Krook, C. Fuchs, R.K. Ramanathan, S.K. Williamson, R.F. Morton, B.P. Findlay, Chemotherapy permits resection of metastatic colorectal cancer: experience from Intergroup N9741. Ann. Oncol. 16, 425–429 (2005)

    Article  PubMed  CAS  Google Scholar 

  7. Network National Comprehensive Cancer, Network National Comprehensive Cancer. Clinical practice guidelines in oncology, ovarian cancer including fallopian tube cancer and primary peritoneal cancer version 2. Clinical Practice Guidelines in Oncology. (2011).

  8. S. Heinrich, M. Schäfer, A. Weber, T.F. Hany, U. Bhure, B.C. Pestalozzi, P. Clavien, Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective phase II trial. Ann. Surg. 248, 1014–1022 (2008)

    Article  PubMed  Google Scholar 

  9. S. Burdett, L. Stewart, Rydzewska, Chemotherapy and surgery versus surgery alone in non-small cell lung cancer. Cochrane Database Syst Rev. (2007).

  10. J. Neoptolemos, J. Dunn, D. Stocken, J. Almond, K. Link, H. Beger, C. Bassi, M. Falconi, P. Pederzoli, C. Dervenis, L. Fernandez-Cruz, F. Lacaine, A. Pap, D. Spooner, D. Kerr, H. Friess, M. Büchler, Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 358, 1576–1585 (2001)

    Article  PubMed  CAS  Google Scholar 

  11. J. Pignon, H. Tribodet, G. Scagliotti, J. Douillard, F. Shepherd, R. Stephens, A. Dunant, V. Torri, R. Rosell, L. Seymour, S.G. Spiro, E. Rolland, R. Fossati, D. Aubert, K. Ding, D. Waller, T. Le Chevalier, Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J. Clin. Oncol. 26, 3552–3559 (2008)

    Article  PubMed  Google Scholar 

  12. G. Bonadonna, E. Brusamolino, P. Valagussa, A. Rossi, L. Brugnatelli, C. Brambilla, M. De Lena, G. Tancini, E. Bajetta, R. Musumeci, U. Veronesi, Combination chemotherapy as an adjuvant treatment in operable breast cancer. N. Engl. J. Med. 294, 405–410 (1976)

    Article  PubMed  CAS  Google Scholar 

  13. R. Gray, J. Barnwell, C. McConkey, R. Hills, N. Williams, D. Kerr, Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 370, 2020–2029 (2007)

    Article  PubMed  Google Scholar 

  14. S. Wöhrer, M. Raderer, M. Hejna, Palliative chemotherapy for advanced gastric cancer. Ann. Oncol. 15, 1585–1595 (2004)

    Article  PubMed  Google Scholar 

  15. P. Simmonds, Palliative chemotherapy for advanced colorectal cancer: systematic review and meta-analysis. Colorectal Cancer Collaborative Group. BMJ 321, 531–535 (2000)

    Article  PubMed  CAS  Google Scholar 

  16. I. Smith, Palliative chemotherapy for advanced non-small cell lung cancer. BMJ. 308, 429–430 (1994)

    Article  PubMed  CAS  Google Scholar 

  17. T. Petit, C. Borel, J.P. Ghnassia, J.F. Rodier, A. Escande, R. Mors, P. Haegelé, Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting. Clin. Cancer Res. 7, 1577–1581 (2001)

    PubMed  CAS  Google Scholar 

  18. F. Penault-Llorca, A. Vincent-Salomon, Roles of the pathologist in neoadjuvant chemotherapy: evaluation of response, prognostic and predictive factors. Ann Pathol. 23, 555–563 (2003)

    PubMed  Google Scholar 

  19. M.G. Daidone, R. Silvestrini, A. Luisi, M. Mastore, E. Benini, S. Veneroni, C. Brambilla, L. Ferrari, M. Greco, S. Andreola, Changes in biological markers after primary chemotherapy for breast cancers. Int. J. Cancer. 61, 301–305 (1995)

    Article  PubMed  CAS  Google Scholar 

  20. V. Cavaillès, A. Gompel, M.C. Portois, S. Thénot, N. Mabon, F. Vignon, Comparative activity of pulsed or continuous estradiol exposure on gene expression and proliferation of normal and tumoral human breast cells. J. Mol. Endocrinol. 28, 165–175 (2002)

    Article  PubMed  Google Scholar 

  21. D. Hanahan, R.A. Weinberg, Hallmarks of cancer: the next generation. Cell. 144, 646–674 (2011)

    Article  PubMed  CAS  Google Scholar 

  22. M. Allen, J. Jones, Jekyll and Hyde: the role of the microenvironment on the progression of cancer. J. Pathol. 223, 162–176 (2011)

    PubMed  CAS  Google Scholar 

  23. B. Elenbaas, R.A. Weinberg, Heterotypic signaling between epithelial tumor cells and fibroblasts in carcinoma formation. Exp. Cell Res. 264, 169–184 (2001)

    Article  PubMed  CAS  Google Scholar 

  24. T.D. Tlsty, P.W. Hein, Know thy neighbor: stromal cells can contribute oncogenic signals. Curr. Opin. Genet. Dev. 11, 54–59 (2001)

    Article  PubMed  CAS  Google Scholar 

  25. A.F. Olumi, G.D. Grossfeld, S.W. Hayward, P.R. Carroll, T.D. Tlsty, G.R. Cunha, Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 59, 5002–5011 (1999)

    PubMed  CAS  Google Scholar 

  26. H. Kiaris, I. Chatzistamou, C. Kalofoutis, H. Koutselini, C. Piperi, A. Kalofoutis, Tumour-stroma interactions in carcinogenesis: basic aspects and perspectives. Mol. Cell. Biochem. 261, 117–122 (2004)

    Article  PubMed  CAS  Google Scholar 

  27. A. Orimo, P.B. Gupta, D.C. Sgroi, F. Arenzana-Seisdedos, T. Delaunay, R. Naeem, V.J. Carey, A.L. Richardson, R A Weinberg, Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell. 121, 335–348 (2005)

    Article  PubMed  CAS  Google Scholar 

  28. N.P. West, M. Dattani, P. Mcshane, G. Hutchins, J. Grabsch, W. Mueller, D. Treanor, P. Quirke, The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients. Br. J. Cancer. 102, 1519–1523 (2010)

    Article  PubMed  CAS  Google Scholar 

  29. A. Labiche, N. Heutte, P. Herlin, J. Chasle, P. Gauduchon, N. Elie, Stromal compartment as a survival prognostic factor in advanced ovarian carcinoma. Int. J. Gynecol. Cancer. 20, 28–33 (2010)

    Article  PubMed  Google Scholar 

  30. Y. Wu, H. Grabsch, T. Ivanova, I.B. Tan, J. Murray, C.H. Ooi, A.I. Wright, Nicholas P West, G.G.A. Hutchins, J. Wu, M. Lee, J. Lee, J.H. Koo, K.G. Yeoh, N. van Grieken, B. Ylstra, S.Y. Rha, J.A. Ajani, J.H. Cheong, S.H. Noh, et al., Comprehensive genomic meta-analysis identifies intra-tumoural stroma as a predictor of survival in patients with gastric cancer. Gut. (2012).

  31. E.M. De Kruijf, J.G.H. van Nes, C.J.H. van de Velde, H. Putter, V.T.H.B.M. Smi, G.J. Liefers, P.J.K. Kuppen, R.A. Tollenaar, W.E. Mesker, Tumor-stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients. Breast Cancer Res. Treat. 125, 687–696 (2011)

    Article  PubMed  Google Scholar 

  32. E.F.W. Courrech Staal, V.T.H.B.M. Smit, M.-L.F. van Velthuysen, J.M.J. Spitzer-Naaykens, M.W.J.M. Wouters, W.E. Mesker, R.A. Tollenaar, J.W. van Sandick, Reproducibility and validation of tumour stroma ratio scoring on oesophageal adenocarcinoma biopsies. Eur. J. Cancer. 47, 375–382 (2011)

    Article  PubMed  Google Scholar 

  33. Y. Zhang, H. Tang, J. Cai, T. Zhang, J. Guo, D. Feng, Z. Wang, Ovarian cancer-associated fibroblasts contribute to epithelial ovarian carcinoma metastasis by promoting angiogenesis, lymphangiogenesis and tumor cell invasion. Cancer Lett. 303, 47–55 (2011)

    Article  PubMed  CAS  Google Scholar 

  34. R. Kalluri, M. Zeisberg, Fibroblasts in cancer. Nat. Rev. Cancer. 6, 392–401 (2006)

    Article  PubMed  CAS  Google Scholar 

  35. T. Sethi, R.C. Rintoul, S.M. Moore, A.C. MacKinnon, D. Salter, C. Choo, E.R. Chilvers, I. Dransfield, S.C. Donnelly, R. Strieter, C. Haslett, Extracellular matrix proteins protect small cell lung cancer cells against apoptosis: a mechanism for small cell lung cancer growth and drug resistance in vivo. Nat. Med. 5, 662–668 (1999)

    Article  PubMed  CAS  Google Scholar 

  36. F. Andre, N. Berrada, C. Desmedt, Implication of tumor microenvironment in the resistance to chemotherapy in breast cancer patients. Curr Opin Oncol. 22, 547–551 (2010)

    Article  PubMed  CAS  Google Scholar 

  37. A. Ostman, M. Augsten, Cancer-associated fibroblasts and tumor growth–bystanders turning into key players. Curr. Opin. Genet. Dev. 19, 67–73 (2009)

    Article  PubMed  CAS  Google Scholar 

  38. K. Pietras, K. Rubin, T. Sjöblom, T. Sjo, E. Buchdunger, M. Sjo, Inhibition of PDGF receptor signaling in tumor stroma enhances antitumor effect of chemotherapy. Cancer Res. 62, 5476–5484 (2002)

    PubMed  CAS  Google Scholar 

  39. K. Pietras, A. Östman, M. Sjöquist, M. Sjo, O. Arne, E. Buchdunger, R.K. Reed, C. Heldin, K. Rubin, Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumors. Cancer Res. 61, 2929–2934 (2001)

    PubMed  CAS  Google Scholar 

  40. M. Sonnenberg, H. van der Kuip, S. Haubeis, P. Fritz, W. Schroth, G. Friedel, W. Simon, T.E. Mürdter, W.E. Aulitzky, Highly variable response to cytotoxic chemotherapy in carcinoma-associated fibroblasts (CAFs) from lung and breast. BMC cancer. 8, 364 (2008)

    Article  PubMed  CAS  Google Scholar 

  41. D. Lafkas, G. Trimis, A.G. Papavassiliou, Hippokratis Kiaris, P53 mutations in stromal fibroblasts sensitize tumors against chemotherapy. Int. J. Cancer. 123, 967–971 (2008)

    Article  PubMed  CAS  Google Scholar 

  42. I. Nakajima, Immunohistochemical study of the extracellular matrix in non-small cell lung cancer: relation to lymph node metastasis and prognosis. Hokkaido Igaku Zasshi. 66, 356–368 (1991)

    PubMed  CAS  Google Scholar 

  43. W.E. Mesker, J.M.C. Junggeburt, K. Szuhai, P. de Heer, H. Morreau, H.J. Tanke, R.A. Tollenaar, The carcinoma-stromal ratio of colon carcinoma is an independent factor for survival compared to lymph node status and tumor stage. Cell. Oncol. 29, 387–398 (2007)

    PubMed  Google Scholar 

  44. A.M. Maeshima, T. Niki, A. Maeshima, T. Yamada, H. Kondo, Y. Matsuno, Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma. Cancer. 95, 2546–2554 (2002)

    Article  PubMed  Google Scholar 

  45. E.F.W. Courrech Staal, M.W.J.M. Wouters, J.W. van Sandick, M.M. Takkenberg, V.T.H.B.M. Smit, J.M.C. Junggeburt, J.M.J. Spitzer-Naaykens, T. Karsten, H.H. Hartgrink, W.E. Mesker, R.A. Tollenaar, The stromal part of adenocarcinomas of the oesophagus: does it conceal targets for therapy? Eur. J. Cancer 46, 720–728 (2010)

    Article  PubMed  Google Scholar 

  46. N. Yanagisawa, R. Li, D. Rowley, H. Liu, D. Kadmon, B.J. Miles, T.M. Wheeler, G.E. Ayala, Stromogenic prostatic carcinoma pattern (carcinomas with reactive stromal grade 3) in needle biopsies predicts biochemical recurrence-free survival in patients after radical prostatectomy. Human pathology. 39, 282–291 (2008)

    Article  PubMed  Google Scholar 

  47. G. Ayala, J.A. Tuxhorn, T.M. Wheeler, A. Frolov, P.T. Scardino, M. Ohori, M. Wheeler, J. Spitler, D.R. Rowley, Reactive stroma as a predictor of biochemical-free recurrence in prostate cancer. Clin. Cancer Res. 9, 4792–4801 (2003)

    PubMed  CAS  Google Scholar 

  48. F. Xing, J. Saidou, K. Watabe, Cancer associated fibroblasts (CAFs) in tumor microenvironment. Front. Biosci. 15, 166–179 (2010)

    Article  PubMed  CAS  Google Scholar 

  49. O. De Wever, P. Demetter, M. Mareel, M. Bracke, Stromal myofibroblasts are drivers of invasive cancer growth. Int. J. Cancer. 123, 2229–2238 (2008)

    Article  PubMed  CAS  Google Scholar 

  50. K. Pietras, A. Ostman, Hallmarks of cancer: interactions with the tumor stroma. Exp. Cell Res. 316, 1324–1331 (2010)

    Article  PubMed  CAS  Google Scholar 

  51. O.E. Franco, A.K. Shaw, D.W. Strand, S.W. Hayward, Cancer associated fibroblasts in cancer pathogenesis. Semin. Cell Dev. Biol. 21, 33–39 (2010)

    Article  PubMed  CAS  Google Scholar 

  52. K. Räsänen, A. Vaheri, Activation of fibroblasts in cancer stroma. Exp. Cell Res. 316, 2713–2722 (2010)

    Article  PubMed  CAS  Google Scholar 

  53. T. Hasebe, S. Sasaki, S. Imoto, A. Ochiai, Highly proliferative fibroblasts forming fibrotic focus govern metastasis of invasive ductal carcinoma of the breast. Mod. Pathol. 14(325–37) (2001)

    Google Scholar 

  54. T. Hasebe, H. Tsuda, S. Hirohashi, Y. Shimosato, Y. Tsubono, H. Yamamoto, K. Mukai, Fibrotic focus in infiltrating ductal carcinoma of the breast: a significant histopathological prognostic parameter for predicting the long-term survival of the patients. Breast Cancer Res. Treat. 49(195–208) (1998)

    Google Scholar 

  55. T. Hasebe, S. Sasaki, S. Imoto, K. Mukai, T. Yokose, A. Ochiai, Prognostic significance of fibrotic focus in invasive ductal carcinoma of the breast: a prospective observational study. Mod. Pathol. 15(502–16) (2002)

    Google Scholar 

  56. J.P.A. Baak, C.G.A. Colpaert, P.J. van Diest, E. Janssen, B. van Diermen, E. Albernaz, P.B. Vermeulen, E.A. Van Marck, Multivariate prognostic evaluation of the mitotic activity index and fibrotic focus in node-negative invasive breast cancers. Eur. J. Cancer. 41, 2093–2101 (2005)

    Article  PubMed  Google Scholar 

  57. C. Colpaert, P. Vermeulen, P. van Beest, G. Goovaerts, J. Weyler, P. Van Dam, L. Dirix, E. Van Marck, Intratumoral hypoxia resulting in the presence of a fibrotic focus is an independent predictor of early distant relapse in lymph node-negative breast cancer patients. Histopathology. 39, 416–425 (2001)

    Article  PubMed  CAS  Google Scholar 

  58. T. Hasebe, S. Sasaki, S. Imoto, A. Ochiai, Proliferative activity of intratumoral fibroblasts is closely correlated with lymph node and distant organ metastases of invasive ductal carcinoma of the breast. Am. J. Pathol. 156(1701–10) (2000)

    Google Scholar 

  59. C. Wenger, V. Ellenrieder, B. Alber, U. Lacher, A. Menke, H. Hameister, M. Wilda, T. Iwamura, H.G. Beger, G. Adler, T.M. Gress, Expression and differential regulation of connective tissue growth factor in pancreatic cancer cells. Oncogene. 18, 1073–1080 (1999)

    Article  PubMed  CAS  Google Scholar 

  60. L.F. Lau, S.C. Lam, The CCN family of angiogenic regulators: the integrin connection. Exp. Cell Res. 248, 44–57 (1999)

    Article  PubMed  CAS  Google Scholar 

  61. F. Yang, J.A. Tuxhorn, S.J. Ressler, S.J. McAlhany, T.D. Dang, D.R. Rowley, Stromal expression of connective tissue growth factor promotes angiogenesis and prostate cancer tumorigenesis. Cancer Res. 65, 8887–8895 (2005)

    Article  PubMed  CAS  Google Scholar 

  62. K.S. Frazier, G.R. Grotendorst, Expression of connective tissue growth factor mRNA in the fibrous stroma of mammary tumors. Int J Biochem Cell Biol. 29, 153–161 (1997)

    Article  PubMed  CAS  Google Scholar 

  63. A. Koliopanos, Helmut Friess, F.F. di Mola, W.-H. Tang, D. Kubulus, D. Brigstock, A. Zimmermann, M.W. Büchler, Connective tissue growth factor gene expression alters tumor progression in esophageal cancer. World J Surg. 26, 420–427 (2002)

    Article  PubMed  Google Scholar 

  64. A.B. Kasaragod, M.S. Lucia, G. Cabirac, G.R. Grotendorst, K.R. Stenmark, Connective tissue growth factor expression in pediatric myofibroblastic tumors. Pediatr. Dev. Pathol. 4, 37–45

  65. T. Shakunaga, T. Ozaki, N. Ohara, K. Asaumi, T. Doi, K. Nishida, A. Kawai, T. Nakanishi, M. Takigawa, H. Inoue, Expression of connective tissue growth factor in cartilaginous tumors. Cancer. 89, 1466–1473 (2000)

    Article  PubMed  CAS  Google Scholar 

  66. M.-Y. Wang, P.-S. Chen, E. Prakash, H.-C. Hsu, H.-Y. Huang, M.-T. Lin, K.-J. Chang, M.-L. Kuo, Connective tissue growth factor confers drug resistance in breast cancer through concomitant up-regulation of Bcl-xL and cIAP1. Cancer Res. 69, 3482–3491 (2009)

    Article  PubMed  CAS  Google Scholar 

  67. M.P. Alfaro, D.L. Deskins, M. Wallus, J. Dasgupta, J.M. Davidson, L.B. Nanney, M. A Guney, M. Gannon, P.P. Young, A physiological role for connective tissue growth factor in early wound healing. Lab. Invest. [Epub ahead of print] (2012).

  68. J. Taylor-Papadimitriou, J. Burchell, J. Hurst, Production of fibronectin by normal and malignant human mammary epithelial cells. Cancer Res. 41, 2491–2500 (1981)

    PubMed  CAS  Google Scholar 

  69. C.-W. Pan, Z.-J. Shen, T.-T. Wu, X.-Y. Tang, M. Wang, J. Sun, Y. Shao, Cell adhesion to fibronectin induces mitomycin C resistance in bladder cancer cells. BJU international. 104, 1774–1779 (2009)

    Article  PubMed  CAS  Google Scholar 

  70. F. Thomas, J.M.P. Holly, R. Persad, A. Bahl, C.M. Perks, Fibronectin confers survival against chemotherapeutic agents but not against radiotherapy in DU145 prostate cancer cells: involvement of the insulin like growth factor-1 receptor. Prostate. 70, 856–865 (2010)

    PubMed  CAS  Google Scholar 

  71. P.S. Hodkinson, T. Elliott, W.S. Wong, R.C. Rintoul, A.C. Mackinnon, C. Haslett, T. Sethi, ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Cell Death Differ. 13, 1776–1788 (2006)

    Article  PubMed  CAS  Google Scholar 

  72. H. Miyamoto, T. Murakami, K. Tsuchida, H. Sugino, H. Miyake, S. Tashiro, Tumor-stroma interaction of human pancreatic cancer: acquired resistance to anticancer drugs and proliferation regulation is dependent on extracellular matrix proteins. Pancreas. 28, 38–44 (2004)

    Article  PubMed  CAS  Google Scholar 

  73. W.S. Argraves, L.M. Greene, M.A. Cooley, W.M. Gallagher, Fibulins: physiological and disease perspectives. EMBO reports. 4, 1127–1131 (2003)

    Article  PubMed  CAS  Google Scholar 

  74. A.J. Obaya, S. Rua, A. Moncada-Pazos, S. Cal, The dual role of fibulins in tumorigenesis. Cancer letters. 325, 132–138 (2012)

    Article  PubMed  CAS  Google Scholar 

  75. S.M. Pupa, S. Giuffré, F. Castiglioni, L. Bertola, M. Cantú, I. Bongarzone, P. Baldassari, R. Mortarini, W.S. Argraves, A. Anichini, S. Menard, E. Tagliabue, Regulation of breast cancer response to chemotherapy by fibulin-1. Cancer Res. 67, 4271–4277 (2007)

    Article  PubMed  CAS  Google Scholar 

  76. A. Sadr-Nabavi, J. Ramser, J. Volkmann, J. Naehrig, F. Wiesmann, B. Betz, H. Hellebrand, S. Engert, S. Seitz, R. Kreutzfeld, T. Sasaki, N. Arnold, R. Schmutzler, M. Kiechle, D. Niederacher, N. Harbeck, E. Dahl, A. Meindl, Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker. Int. J. Cancer. 124, 1727–1735 (2009)

    Article  PubMed  CAS  Google Scholar 

  77. E.F. Roark, D.R. Keene, C.C. Haudenschild, S. Godyna, C.D. Little, W S Argraves, The association of human fibulin-1 with elastic fibers: an immunohistological, ultrastructural, and RNA study. J. Histochem. Cytochem. 43, 401–411 (1995)

    Article  PubMed  CAS  Google Scholar 

  78. A.R. Albig, J.R. Neil, W.P. Schiemann, Fibulins 3 and 5 antagonize tumor angiogenesis in vivo. Cancer Res. 66, 2621–2629 (2006)

    Article  PubMed  CAS  Google Scholar 

  79. R.K. Sironen, M. Tammi, R. Tammi, P.K. Auvinen, M. Anttila, V.-M. Kosma, Hyaluronan in human malignancies. Exp. Cell Res. 317, 383–391 (2011)

    Article  PubMed  CAS  Google Scholar 

  80. R.H. Tammi, A. Kultti, Veli-Matti Kosma, R. Pirinen, P. Auvinen, M.I. Tammi, Hyaluronan in human tumors: pathobiological and prognostic messages from cell-associated and stromal hyaluronan. Semin. Cancer Biol. 18, 288–295 (2008)

    Article  PubMed  CAS  Google Scholar 

  81. P. Gibbs, P.R. Clingan, V. Ganju, A.H. Strickland, S.S. Wong, N.C. Tebbutt, C.R. Underhill, R.M. Fox, S.P. Clavant, J. Leung, M. Pho, T.J. Brown, Hyaluronan-Irinotecan improves progression-free survival in 5-fluorouracil refractory patients with metastatic colorectal cancer: a randomized phase II trial. Cancer Chemother. Pharmacol. 67, 153–163 (2011)

    Article  PubMed  CAS  Google Scholar 

  82. Y. Xie, K.L. Aillon, S. Cai, J.M. Christian, N.M. Davies, C.J. Berkland, M.L. Forrest, Pulmonary delivery of cisplatin-hyaluronan conjugates via endotracheal instillation for the treatment of lung cancer. Int J Pharm. 392, 156–163 (2010)

    Article  PubMed  CAS  Google Scholar 

  83. S. Misra, S. Ghatak, B.P. Toole, Regulation of MDR1 expression and drug resistance by a positive feedback loop involving hyaluronan, phosphoinositide 3-kinase, and ErbB2. J. Biol. Chem. 280, 20310–20315 (2005)

    Article  PubMed  CAS  Google Scholar 

  84. P. Auvinen, R. Tammi, J. Parkkinen, M. Tammi, U. Agren, R. Johansson, P. Hirvikoski, M. Eskelinen, V.M. Kosma, Hyaluronan in peritumoral stroma and malignant cells associates with breast cancer spreading and predicts survival. Am. J. Pathol. 156(529–36) (2000)

    Google Scholar 

  85. R. Pirinen, R. Tammi, M. Tammi, P. Hirvikoski, J.J. Parkkinen, R. Johansson, J. Böhm, S. Hollmén, V.M. Kosma, Prognostic value of hyaluronan expression in non-small-cell lung cancer: Increased stromal expression indicates unfavorable outcome in patients with adenocarcinoma. Int. J. Cancer. 95(12–7) (2001)

    Google Scholar 

  86. K. Matsumoto, K. Date, H. Ohmichi, T. Nakamura, Hepatocyte growth factor in lung morphogenesis and tumor invasion: role as a mediator in epithelium-mesenchyme and tumor-stroma interactions. Cancer Chemother. Pharmacol. 38(Suppl), S42–S47 (1996)

    Article  PubMed  CAS  Google Scholar 

  87. J. Yamashita, M. Ogawa, S. Yamashita, K. Nomura, M. Kuramoto, T. Saishoji, Immunoreactive hepatocyte growth factor is a strong and independent predictor of recurrence and survival in human breast cancer. Cancer. 54, 1630–1633 (1994)

    CAS  Google Scholar 

  88. Q. Zeng, S. Chen, Z. You, Y. Fan, T.E. Carey, D. Saims, C.-Y. Wang, Hepatocyte growth factor inhibits anoikis in head and neck squamous cell carcinoma cells by activation of ERK and Akt signaling independent of NFkappa. B. J. Biol. Chem 277, 25203–25208 (2002)

    Article  CAS  Google Scholar 

  89. S. Fan, J.A. Wang, R.Q. Yuan, S. Rockwell, J. Andres, A. Zlatapolskiy, I.D. Goldberg, E.M. Rosen, Scatter factor protects epithelial and carcinoma cells against apoptosis induced by DNA-damaging agents. Oncogene. 17, 131–141 (1998)

    Article  PubMed  CAS  Google Scholar 

  90. M. Mildner, L. Eckhart, B. Lengauer, E. Tschachler, Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human keratinocytes but not of keratinocyte-derived cell lines via the phosphatidylinositol 3-kinase/AKT pathway. J. Biol. Chem. 277, 14146–14152 (2002)

    Article  PubMed  CAS  Google Scholar 

  91. A. Rasola, Hepatocyte growth factor sensitizes human ovarian carcinoma cell lines to paclitaxel and cisplatin. Cancer Res. 64, 1744–1750 (2004)

    Article  PubMed  CAS  Google Scholar 

  92. L.A. Shuman Moss, S. Jensen-Taubman, W.G. Stetler-Stevenson, Matrix metalloproteinases: changing roles in tumor progression and metastasis. Am. J. Pathol. 181, 1895–1899 (2012)

    Article  PubMed  CAS  Google Scholar 

  93. R. Poulsom, M. Pignatelli, W.G. Stetler-Stevenson, L.A. Liotta, P.A. Wright, R.E. Jeffery, J.M. Longcroft, L. Rogers, G.W. Stamp, Stromal expression of 72 kda type IV collagenase (MMP-2) and TIMP-2 mRNAs in colorectal neoplasia. Am. J. Pathol. 141(389–96) (1992)

    Google Scholar 

  94. C. Pyke, E. Ralfkiaer, K. Tryggvason, K. Danø, Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. Am. J. Pathol. 142, 359–365 (1993)

    PubMed  CAS  Google Scholar 

  95. H. Liu, T. Zhang, X. Li, J. Huang, B. Wu, X. Huang, Y. Zhou, J. Zhu, J. Hou, Predictive value of MMP-7 expression for response to chemotherapy and survival in patients with non-small cell lung cancer. Cancer Sci. 99(2185–92) (2008)

    Google Scholar 

  96. G.I. Murray, M.E. Duncan, P. O’Neil, J.A. McKay, W.T. Melvin, J.E. Fothergill, Matrix metalloproteinase-1 is associated with poor prognosis in oesophageal cancer. J. Pathol. 185, 256–261 (1998)

    Article  PubMed  CAS  Google Scholar 

  97. B. Fingleton, T. Vargo-Gogola, H.C. Crawford, L.M. Matrisian, Matrilysin [MMP-7] expression selects for cells with reduced sensitivity to apoptosis. Neoplasia. 3, 459–68

  98. N. Mitsiades, W.H. Yu, V. Poulaki, M. Tsokos, I. Stamenkovic, Matrix metalloproteinase-7-mediated cleavage of Fas ligand protects tumor cells from chemotherapeutic drug cytotoxicity. Cancer Res. 61, 577–581 (2001)

    PubMed  CAS  Google Scholar 

  99. V. Almendro, E. Ametller, S. García-Recio, O. Collazo, I. Casas, J.M. Augé, J. Maurel, P. Gascón, The role of MMP7 and its cross-talk with the FAS/FASL system during the acquisition of chemoresistance to oxaliplatin. PloS ONE. 4, e4728 (2009)

    Article  PubMed  CAS  Google Scholar 

  100. M. Egeblad, Z. Werb, New functions for the matrix metalloproteinases in cancer progression. Nature reviews. Nature reviews. Cancer. 2, 161–174 (2002)

    Article  PubMed  CAS  Google Scholar 

  101. Y. Jiang, I.D. Goldberg, Y.E. Shi, Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21, 2245–2252 (2002)

    Article  PubMed  CAS  Google Scholar 

  102. M.N. Holten-Andersen, U. Hansen, N. Brünner, H.J. Nielsen, M. Illemann, B.S. Nielsen, Localization of tissue inhibitor of metalloproteinases 1 (TIMP-1) in human colorectal adenoma and adenocarcinoma. Int. J. Cancer. 113, 198–206 (2005)

    Article  PubMed  CAS  Google Scholar 

  103. A.-S. Schrohl, M.E. Meijer-van Gelder, M.N. Holten-Andersen, I.J. Christensen, M.P. Look, H.T. Mouridsen, N. Brünner, J.A. Foekens, Primary tumor levels of tissue inhibitor of metalloproteinases-1 are predictive of resistance to chemotherapy in patients with metastatic breast cancer. Clin. Cancer Res. 12, 7054–7058 (2006)

    Article  PubMed  CAS  Google Scholar 

  104. G.L. Willemoe, P.B. Hertel, A. Bartels, M.-B. Jensen, E. Balslev, B.B. Rasmussen, H. Mouridsen, B. Ejlertsen, N. Brünner, Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n=647) with primary breast cancer. A Danish Breast Cancer Cooperative Group Study. Eur. J. Cancer. 45, 2528–2536 (2009)

    Article  PubMed  CAS  Google Scholar 

  105. N.M. Sørensen, P. Byström, I.J. Christensen, A. Berglund, H.J. Nielsen, N. Brünner, B. Glimelius, TIMP-1 is significantly associated with objective response and survival in metastatic colorectal cancer patients receiving combination of irinotecan, 5-fluorouracil, and folinic acid. Clin. Cancer Res 13, 4117–4122 (2007)

    Article  PubMed  CAS  Google Scholar 

  106. K.D. Steffensen, M. Waldstrøm, R.K. Christensen, A. Bartels, N. Brünner, A. Jakobsen, Lack of relationship between TIMP-1 tumour cell immunoreactivity, treatment efficacy and prognosis in patients with advanced epithelial ovarian cancer. BMC cancer. 10, 185 (2010)

    Article  PubMed  Google Scholar 

  107. A.D. Bradshaw, Diverse biological functions of the SPARC family of proteins. The international journal of biochemistry & cell biology. 44, 480–488 (2012)

    Article  CAS  Google Scholar 

  108. I.T. Tai, M.J. Tang, SPARC in cancer biology: its role in cancer progression and potential for therapy. Drug resistance updates: reviews and commentaries in antimicrobial and anticancer chemotherapy. 11, 231–246 (2008)

    CAS  Google Scholar 

  109. M. Rahman, A.P.K. Chan, I.T. Tai, A peptide of SPARC interferes with the interaction between caspase8 and Bcl2 to resensitize chemoresistant tumors and enhance their regression in vivo. PloS ONE. 6, e26390 (2011)

    Article  PubMed  CAS  Google Scholar 

  110. M.J. Tang, I.T. Tai, A novel interaction between procaspase 8 and SPARC enhances apoptosis and potentiates chemotherapy sensitivity in colorectal cancers. J. Biol. Chem. 282, 34457–34467 (2007)

    Article  PubMed  CAS  Google Scholar 

  111. J.M. Chan, S.H. Ho, I.T. Tai, Secreted protein acidic and rich in cysteine-induced cellular senescence in colorectal cancers in response to irinotecan is mediated by P53. Carcinogenesis. 31, 812–819 (2010)

    Article  PubMed  CAS  Google Scholar 

  112. C. Atorrasagasti, M. Malvicini, J.B. Aquino, L. Alaniz, M. Garcia, M. Bolontrade, M. Rizzo, O.L. Podhajcer, G. Mazzolini, Overexpression of SPARC obliterates the in vivo tumorigenicity of human hepatocellular carcinoma cells. Int. J. Cancer. 126, 2726–2740 (2010)

    PubMed  CAS  Google Scholar 

  113. I.T. Tai, M. Dai, D.A. Owen, L.B. Chen, Genome-wide expression analysis of therapy-resistant tumors reveals SPARC as a novel target for cancer therapy. J. Clin. Invest. 115, 1492–1502 (2005)

    Article  PubMed  CAS  Google Scholar 

  114. S.L. Bull Phelps, J. Carbon, A. Miller, E. Castro-Rivera, S. Arnold, R.A. Brekken, J.S. Lea, Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity. Am. J. Obstet. Gynecol 200, 180.e1–7 (2009)

    Article  CAS  Google Scholar 

  115. H.-C. Jeung, S.Y. Rha, C.K. Im, S.J. Shin, J.B. Ahn, W.I. Yang, J.K. Roh, S.H. Noh, H.C. Chung, A randomized phase 2 study of docetaxel and S-1 versus docetaxel and cisplatin in advanced gastric cancer with an evaluation of SPARC expression for personalized therapy. Cancer. 117, 2050–2057 (2011)

    Article  PubMed  CAS  Google Scholar 

  116. A. Francki, K. Motamed, T.D. McClure, M. Kaya, C. Murri, D.J. Blake, J.G. Carbon, E.H. Sage, SPARC regulates cell cycle progression in mesangial cells via its inhibition of IGF-dependent signaling. J. Cell. Biochem. 88, 802–811 (2003)

    Article  PubMed  CAS  Google Scholar 

  117. B.J. Schiemann, J.R. Neil, W.P. Schiemann, SPARC inhibits epithelial cell proliferation in part through stimulation of the transforming growth factor-beta-signaling system. Mol. Biol. Cell. 14, 3977–3988 (2003)

    Article  PubMed  CAS  Google Scholar 

  118. A. Francki, A.D. Bradshaw, J.A. Bassuk, C.C. Howe, W.G. Couser, E.H. Sage, SPARC regulates the expression of collagen type I and transforming growth factor-beta1 in mesangial cells. J. Cell. Biochem. 274(32145–52) (1999)

    Google Scholar 

  119. M. Bernfield, M. Götte, P.W. Park, O. Reizes, M.L. Fitzgerald, J. Lincecum, M. Zako, Functions of cell surface heparan sulfate proteoglycans. Annu. Rev. Biochem. 68, 729–777 (1999)

    Article  PubMed  CAS  Google Scholar 

  120. M. Götte, Syndecans in inflammation. FASEB J. 17, 575–591 (2003)

    Article  PubMed  Google Scholar 

  121. T. Maeda, C.M. Alexander, A. Friedl, Induction of syndecan-1 expression in stromal fibroblasts promotes proliferation of human breast cancer cells. Cancer Res. 64, 612–621 (2004)

    Article  PubMed  CAS  Google Scholar 

  122. B.J. Burbach, Y. Ji, A.C. Rapraeger, Syndecan-1 ectodomain regulates matrix-dependent signaling in human breast carcinoma cells. Exp. Cell Res. 300, 234–247 (2004)

    Article  PubMed  CAS  Google Scholar 

  123. M. Barbareschi, P. Maisonneuve, D. Aldovini, M.G. Cangi, L. Pecciarini, F. Angelo Mauri, S. Veronese, O. Caffo, A. Lucenti, P.D. Palma, E. Galligioni, C. Doglioni, High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis. Cancer. 98, 474–483 (2003)

    Article  PubMed  Google Scholar 

  124. C. Martin Götte, M. Kersting, J. Ruggiero, A.H. Tio, L. Tulusan, P. Kiesel, Wülfing, Predictive value of syndecan-1 expression for the response to neoadjuvant chemotherapy of primary breast cancer. Anticancer Res. 26, 621–627 (2006)

    PubMed  Google Scholar 

  125. E. Tsanou, E. Ioachim, E. Briasoulis, A. Charchanti, K. Damala, V. Karavasilis, N. Pavlidis, N.J. Agnantis, Clinicopathological study of the expression of syndecan-1 in invasive breast carcinomas. correlation with extracellular matrix components. J. Exp. Clin. Cancer Res. 23, 641–650 (2004)

    PubMed  CAS  Google Scholar 

  126. E.J. Kantelhardt, M. Vetter, M. Schmidt, C. Veyret, D. Augustin, V. Hanf, C. Meisner, D. Paepke, M. Schmitt, F. Sweep, G. von Minckwitz, P.-M. Martin, F. Jaenicke, C. Thomssen, N. Harbeck, Prospective evaluation of prognostic factors uPA/PAI-1 in node-negative breast cancer: phase III NNBC3-Europe trial (AGO, GBG, EORTC-PBG) comparing 6 × FEC versus 3 × FEC/3 × Docetaxel. BMC cancer. 11, 140 (2011)

    Article  PubMed  CAS  Google Scholar 

  127. E. Dublin, A. Hanby, N.K. Patel, R. Liebman, D. Barnes, Immunohistochemical expression of uPA, uPAR, and PAI-1 in breast carcinoma. Fibroblastic expression has strong associations with tumor pathology. Am. J. Pathol. 157, 1219–1227 (2000)

    Article  PubMed  CAS  Google Scholar 

  128. N. Harbeck, R.E. Kates, M. Schmitt, Clinical relevance of invasion factors urokinase-type plasminogen activator and plasminogen activator inhibitor type 1 for individualized therapy decisions in primary breast cancer is greatest when used in combination. J. Clin. Oncol. 20(1000–7) (2002)

    Google Scholar 

  129. N. Harbeck, R.E. Kates, M.P. Look, M. Kiechle, F. Ja, M. Schmitt, J.A. Foekens, Enhanced Benefit from Adjuvant Chemotherapy in Breast Cancer Patients Classified High-Risk according to Urokinase-type Plasminogen Activator (uPA) and Plasminogen Activator Inhibitor Type 1 (n = 3424. Cancer Res. 62(4617–22) (2002)

    Google Scholar 

  130. P. Manders, V.C.G. Tjan-Heijnen, P.N. Span, N. Grebenchtchikov, A.J. Geurts-Moespot, D.T.H. van Tienoven, L.V.A.M. Beex, F.C.G.J. Sweep, The complex between urokinase-type plasminogen activator (uPA) and its type-1 inhibitor (PAI-I) independently predicts response to first-line endocrine therapy in advanced breast cancer. Thromb. Haemost. 91, 514–521 (2004)

    PubMed  CAS  Google Scholar 

  131. S. Borstnar, A. Sadikov, B. Mozina, T. Cufer, High levels of uPA and PAI-1 predict a good response to anthracyclines. Breast Cancer Res. Treat. 121, 615–624 (2010)

    Article  PubMed  CAS  Google Scholar 

  132. P. Manders, Predictive impact of urokinase-type plasminogen activator: plasminogen activator inhibitor type-1 complex on the efficacy of adjuvant systemic therapy in primary breast cancer. Cancer Res. 64, 659–664 (2004)

    Article  PubMed  CAS  Google Scholar 

  133. S. Ohno, M. Tachibana, T. Fujii, S. Ueda, H. Kubota, N. Nagasue, Role of stromal collagen in immunomodulation and prognosis of advanced gastric carcinoma. Int. J. Cancer. 97, 770–774 (2002)

    Article  PubMed  CAS  Google Scholar 

  134. N. Harbeck, R.E. Kates, M. Schmitt, K. Gauger, M. Kiechle, F. Jänicke, C. Thomssen, M.P. Look, J.A. Foekens, Urokinase-type plasminogen activator and its inhibitor type 1 predict disease outcome and therapy response in primary breast cancer. Clin. Breast Cancer 5, 348–352 (2004)

    Article  PubMed  CAS  Google Scholar 

  135. S. McAllister, A. Gifford, A. Greiner, S. Kelleher, M. Saelzler, T. Ince, F. Reinhardt, L. Harris, B. Hylander, E. Repasky, R. Weinberg, Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell. 133, 994–1005 (2008)

    Article  PubMed  CAS  Google Scholar 

  136. A.S. Schrohl, I.J. Christensen, A.N. Pedersen, V. Jensen, H. Mouridsen, G. Murphy, J.A. Foekens, N. Brunner, Mads Nikolaj Holten-Andersen, Tumor tissue concentrations of the proteinase inhibitors tissue inhibitor of metalloproteinases-1 (TIMP-1) and plasminogen activator inhibitor type 1 (PAI-1) are complementary in determining prognosis in primary breast cancer. Mol. Cell Proteomics. 2(164–72) (2003)

    Google Scholar 

  137. F. Jänicke, A. Prechtl, C. Thomssen, N. Harbeck, C. Meisner, M. Untch, C.G. Sweep, H.K. Selbmann, H. Graeff, M. Schmitt, Randomized adjuvant chemotherapy trial in high-risk, lymph node-negative breast cancer patients identified by urokinase-type plasminogen activator and plasminogen activator inhibitor type 1. J. Natl. Cancer Inst. 93(913–20) (2001)

    Google Scholar 

  138. C. Chuaysri, P. Thuwajit, A. Paupairoj, S. Chau-In, T. Suthiphongchai, C. Thuwajit, Alpha-smooth muscle actin-positive fibroblasts promote biliary cell proliferation and correlate with poor survival in cholangiocarcinoma. Oncol. Rep. 21, 957–969 (2009)

    PubMed  CAS  Google Scholar 

  139. T. Tsujino, I. Seshimo, Hirofumi Yamamoto, C.Y. Ngan, K. Ezumi, I. Takemasa, M. Ikeda, M. Sekimoto, N. Matsuura, M. Monden, Stromal myofibroblasts predict disease recurrence for colorectal cancer. Clin. Cancer Res. 13, 2082–2090 (2007)

    Article  PubMed  CAS  Google Scholar 

  140. M. Erkan, C.W. Michalski, S. Rieder, C. Reiser-Erkan, I. Abiatari, A. Kolb, N.A. Giese, I. Esposito, H. Friess, J. Kleeff, The activated stroma index is a novel and independent prognostic marker in pancreatic ductal adenocarcinoma. Clin. Gastroenterol. Hepatol. 6, 1155–1161 (2008)

    Article  PubMed  Google Scholar 

  141. H. Zhong, A.M. De Marzo, E. Laughner, M. Lim, D.A. Hilton, D. Zagzag, P. Buechler, W.B. Isaacs, G.L. Semenza, J.W. Simons, Overexpression of hypoxia-inducible factor 1 alpha in common human cancers and their metastases. Cancer Res. 59, 5830–5835 (1999)

    PubMed  CAS  Google Scholar 

  142. D.M. Brizel, G.S. Sibley, L.R. Prosnitz, R.L. Scher, M.W. Dewhirst, Tumor hypoxia adversely affects the prognosis of carcinoma of the head and neck. Int. J. Radiat. Oncol. Biol. Phys. 38, 285–289 (1997)

    Article  PubMed  CAS  Google Scholar 

  143. K. Sundfør, H. Lyng, E.K. Rofstad, Tumour hypoxia and vascular density as predictors of metastasis in squamous cell carcinoma of the uterine cervix. Br. J. Cancer. 78, 822–827 (1998)

    Article  PubMed  Google Scholar 

  144. M. Bacac, P. Provero, N. Mayran, J.-C. Stehle, C. Fusco, I. Stamenkovic, A mouse stromal response to tumor invasion predicts prostate and breast cancer patient survival. PloS ONE. 1, e32 (2006)

    Article  PubMed  CAS  Google Scholar 

  145. K. Utispan, P. Thuwajit, Y. Abiko, K. Charngkaew, A. Paupairoj, S. Chau-in, C. Thuwajit, Gene expression profiling of cholangiocarcinoma-derived fibroblast reveals alterations related to tumor progression and indicates periostin as a poor prognostic marker. Mol. Cancer. 9, 13 (2010)

    Article  PubMed  CAS  Google Scholar 

  146. T. Yamanashi, Y. Nakanishi, G. Fujii, Y. Akishima-Fukasawa, Y. Moriya, Y. Kanai, M. Watanabe, S. Hirohashi, Podoplanin expression identified in stromal fibroblasts as a favorable prognostic marker in patients with colorectal carcinoma. Oncology. 77, 53–62 (2009)

    Article  PubMed  CAS  Google Scholar 

  147. M. Leivonen, J. Lundin, S. Nordling, K. von Boguslawski, C. Haglund, Prognostic value of syndecan-1 expression in breast cancer. Oncology. 67, 11–18 (2004)

    Article  PubMed  CAS  Google Scholar 

  148. J.R. Infante, H. Matsubayashi, N. Sato, J. Tonascia, A.P. Klein, T.A. Riall, C. Yeo, C. Iacobuzio-Donahue, M. Goggins, Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J. Clin. Oncol. 25, 319–325 (2007)

    Article  PubMed  Google Scholar 

  149. A.H. Ree, V.A. Florenes, J.P. Berg, G.M. Maelandsmo, J.M. Nesland, O. Fodstad, High levels of messenger RNAs for tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in primary breast carcinomas are associated with development of distant metastases. Clin. Cancer Res. 3, 1623–1628 (1997)

    PubMed  CAS  Google Scholar 

  150. K. McCarthy, T. Maguire, G. McGreal, E. McDermott, N. O’Higgins, M.J. Duffy, High levels of tissue inhibitor of metalloproteinase-1 predict poor outcome in patients with breast cancer. Int. J. Cancer. 84, 44–48 (1999)

    Article  PubMed  CAS  Google Scholar 

  151. M.P. Look, W.L.J. van Putten, M.J. Duffy, N. Harbeck, I.J. Christensen, C. Thomssen, R. Kates, F. Spyratos, M. Fernö, S. Eppenberger-Castori, C.G.J.F. Sweep, K. Ulm, J. Peyrat, P. Martin, H. Magdelenat, N. Brünner, C. Duggan, B.W. Lisboa, P. Bendahl, V. Quillien et al., Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients. J. Natl. Cancer Inst 94, 116–128 (2002)

    Article  PubMed  CAS  Google Scholar 

  152. P.A. Andreasen, L. Kjøller, L. Christensen, M.J. Duffy, The urokinase-type plasminogen activator system in cancer metastasis: a review. Int. J. Cancer. 72, 1–22 (1997)

    Article  PubMed  CAS  Google Scholar 

  153. M. Schmitt, N. Harbeck, C. Thomssen, O. Wilhelm, V. Magdolen, U. Reuning, K. Ulm, H. Höfler, F. Jänicke, H. Graeff, Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb. Haemost. 78(285–96) (1997)

  154. M.J. Duffy, T.M. Maguire, E.W. McDermott, N. O’Higgins, Urokinase plasminogen activator: a prognostic marker in multiple types of cancer. J Surg Oncol. 71(130–5) (1999)

    Google Scholar 

  155. C.Y. Ngan, H. Yamamoto, I. Seshimo, T. Tsujino, M. Man-i, J.-I. Ikeda, K. Konishi, I. Takemasa, M. Ikeda, M. Sekimoto, N. Matsuura, M. Monden, Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer. Br. J. Cancer 96, 986–992 (2007)

    Article  PubMed  CAS  Google Scholar 

  156. S. Al-Saad, K. Al-Shibli, T. Donnem, M. Persson, R.M. Bremnes, L.-T. Busund, The prognostic impact of NF-kappaB p105, vimentin, E-cadherin and Par6 expression in epithelial and stromal compartment in non-small-cell lung cancer. Br. J. Cancer. 99, 1476–1483 (2008)

    Article  PubMed  CAS  Google Scholar 

  157. L.-K. Liu, X.-Y. Jiang, X.-X. Zhou, D.-M. Wang, X.-L. Song, H.-B. Jiang, Upregulation of vimentin and aberrant expression of E-cadherin/beta-catenin complex in oral squamous cell carcinomas: correlation with the clinicopathological features and patient outcome. Mod. Pathol. 23, 213–224 (2010)

    Article  PubMed  CAS  Google Scholar 

  158. S. Otsuki, M. Inokuchi, M. Enjoji, T. Ishikawa, Y. Takagi, K. Kato, H. Yamada, K. Kojima, K. Sugihara, Vimentin expression is associated with decreased survival in gastric cancer. Oncol. Rep. 25, 1235–1242 (2011)

    PubMed  Google Scholar 

  159. T. Hasebe, H. Tsuda, Y. Tsubono, S. Imoto, K. Mukai, Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognostic parameter for tumor recurrence and tumor death within three years after the initial operation. Jpn. J. Cancer Res. 88(590–9) (1997)

    Google Scholar 

  160. A. Neesse, P. Michl, K.K. Frese, C. Feig, N. Cook, M.A. Jacobetz, M.P. Lolkema, M. Buchholz, K.P. Olive, T.M. Gress, D.A. Tuveson, Stromal biology and therapy in pancreatic cancer. Gut 60, 861–868 (2011)

    Article  PubMed  Google Scholar 

  161. I.G. Schauer, A.K. Sood, S. Mok, Cancer-associated fibroblasts and their putative role in potentiating the initiation and development of epithelial ovarian cancer. Neoplasia. 13, 393–405 (2011)

    PubMed  CAS  Google Scholar 

  162. H. Breuninger, G. Schaumburg-Lever, J. Holzschuh, H.P. Horny, Desmoplastic squamous cell carcinoma of skin and vermilion surface: a highly malignant subtype of skin cancer. Cancer. 79, 915–919 (1997)

    Article  PubMed  CAS  Google Scholar 

  163. L.A. Hazlehurst, W.S. Dalton, Mechanisms associated with cell adhesion mediated drug resistance (CAM-DR) in hematopoietic malignancies. Cancer Metastasis Rev. 20, 43–50 (2001)

    Article  PubMed  CAS  Google Scholar 

  164. H.F. Dvorak, Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315, 1650–1659 (1986)

    Article  PubMed  CAS  Google Scholar 

  165. S. Grotegut, R. Kappler, S. Tarimoradi, F. Lehembre, Hepatocyte growth factor protects hepatoblastoma cells from chemotherapy-induced apoptosis by AKT activation. Int. J. Oncol. 36, 1261–1267 (2010)

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was funded by the Jean Shanks Foundation.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Section of Pathology & Tumour Biology, Leeds Institute of Molecular Medicine, University of Leeds, Wellcome Trust Brenner Building, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK

    Matthew David Hale & Heike Irmgard Grabsch

  2. Department of Upper Gastrointestinal Surgery, Leeds Teaching Hospitals NHS Trust, St James’s Institute of Oncology, Bexley Wing, St James’s University Hospital, Beckett Street, Leeds, LS9 7TF, UK

    Jeremy David Hayden

Authors
  1. Matthew David Hale
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeremy David Hayden
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Heike Irmgard Grabsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Heike Irmgard Grabsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hale, M.D., Hayden, J.D. & Grabsch, H.I. Tumour-microenvironment interactions: role of tumour stroma and proteins produced by cancer-associated fibroblasts in chemotherapy response. Cell Oncol. 36, 95–112 (2013). https://doi.org/10.1007/s13402-013-0127-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13402-013-0127-7

Keywords

Search

Navigation