Skip to main content
SpringerLink
Log in

Hypoxia and the Metastatic Niche

  • Chapter
  • First Online:
Hypoxia and Cancer Metastasis

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1136))

Abstract

Metastasis is considered the latest stage of cancer development; however, metastasis occurs earlier than it can be detected. Metastatic sites are actively remodeled by secretory factors including growth factors, chemokines and cytokines, extracellular matrix (ECM) enzymes, and exosomes produced by the primary cancer tissues. Many of the associated-secretory factors are abundantly induced by inflammation and hypoxia. These secretory factors modify the ECM, immune composition, and blood vessel permeability of the future metastatic sites, a process termed ‘metastatic niche formation.’ In general, ECM is modified to enhance the attachment of other cell types or cancer cells to establish a growth-factor rich metastatic niche. Immune-suppressive cells such as tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) dominate the metastatic niche to allow metastatic cancer cells to bypass immune surveillance and propagate. Endothelial cell-to-cell junctions of blood vessels are loosened to enhance the penetrance of metastatic cancer cells to the metastatic sites. Different metastatic tissues have unique ECM constituents, resident immune cells, and anatomical positions linked with the circulatory system; therefore, many cancer types have their own metastatic pattern, and they favor metastasis to specific organs. Some of the remodeling events represent the earliest step of metastasis, even preceding the detachment of cancer cells from the primary tumor site. Understanding how the metastatic niche is formed is important for the development of drugs to prevent the earliest step of metastasis and advance our understanding of organotrophic metastasis. This review summarizes the major findings in the field of metastatic niche highlighting the role of hypoxia.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 109.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Leong SP, Cady B, Jablons DM, Garcia-Aguilar J, Reintgen D, Jakub J, Pendas S, Duhaime L, Cassell R, Gardner M, Giuliano R, Archie V, Calvin D, Mensha L, Shivers S, Cox C, Werner JA, Kitagawa Y, Kitajima M (2006) Clinical patterns of metastasis. Cancer Metastasis Rev 25:221–232

    Article  PubMed  Google Scholar 

  2. Patel JK, Didolkar MS, Pickren JW, Moore RH (1978) Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am J Surg 135:807–810

    Article  CAS  PubMed  Google Scholar 

  3. Bhansali MS, Fujita H, Kakegawa T, Yamana H, Ono T, Hikita S, Toh Y, Fujii T, Tou U, Shirouzu K (1997) Pattern of recurrence after extended radical esophagectomy with three-field lymph node dissection for squamous cell carcinoma in the thoracic esophagus. World J Surg 21:275–281

    Article  CAS  PubMed  Google Scholar 

  4. Mafune KI, Tanaka Y, Takubo K (2000) Autopsy findings in patients with esophageal carcinoma: comparison between resection and nonresection groups. J Surg Oncol 74:196–200

    Article  CAS  PubMed  Google Scholar 

  5. Saito T, Iizuka T, Kato H, Watanabe H (1985) Esophageal carcinoma metastatic to the stomach. A clinicopathologic study of 35 cases. Cancer 56:2235–2241

    Article  CAS  PubMed  Google Scholar 

  6. Kato H, Miyazaki T, Nakajima M, Sohda M, Fukai Y, Masuda N, Fukuchi M, Manda R, Tsukada K, Kuwano H (2003) Prediction of hematogenous recurrence in patients with esophageal carcinoma. Jpn J Thorac Cardiovasc Surg 51:599–608

    Article  PubMed  Google Scholar 

  7. Niederhuber JE (1993) Colon and rectum cancer. Patterns of spread and implications for workup. Cancer 71:4187–4192

    Article  CAS  PubMed  Google Scholar 

  8. Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, Le QT, Giaccia AJ (2009) Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15:35–44

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Gao D, Nolan DJ, Mellick AS, Bambino K, McDonnell K, Mittal V (2008) Endothelial progenitor cells control the angiogenic switch in mouse lung metastasis. Science 319:195–198

    Article  CAS  PubMed  Google Scholar 

  10. Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, MacDonald DD, Jin DK, Shido K, Kerns SA, Zhu Z, Hicklin D, Wu Y, Port JL, Altorki N, Port ER, Ruggero D, Shmelkov SV, Jensen KK, Rafii S, Lyden D (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438:820–827

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Liu C, Yu S, Kappes J, Wang J, Grizzle WE, Zinn KR, Zhang HG (2007) Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood 109:4336–4342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lyden D, Hattori K, Dias S, Costa C, Blaikie P, Butros L, Chadburn A, Heissig B, Marks W, Witte L, Wu Y, Hicklin D, Zhu Z, Hackett NR, Crystal RG, Moore MA, Hajjar KA, Manova K, Benezra R, Rafii S (2001) Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat Med 7:1194–1201

    Article  CAS  PubMed  Google Scholar 

  13. Yang L, DeBusk LM, Fukuda K, Fingleton B, Green-Jarvis B, Shyr Y, Matrisian LM, Carbone DP, Lin PC (2004) Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell 6:409–421

    Article  CAS  PubMed  Google Scholar 

  14. Pollard JW (2009) Trophic macrophages in development and disease. Nat Rev Immunol 9:259–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Qian BZ, Pollard JW (2010) Macrophage diversity enhances tumor progression and metastasis. Cell 141:39–51

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Chen JJ, Lin YC, Yao PL, Yuan A, Chen HY, Shun CT, Tsai MF, Chen CH, Yang PC (2005) Tumor-associated macrophages: the double-edged sword in cancer progression. J Clin Oncol 23:953–964

    Article  CAS  PubMed  Google Scholar 

  17. Ryder M, Ghossein RA, Ricarte-Filho JC, Knauf JA, Fagin JA (2008) Increased density of tumor-associated macrophages is associated with decreased survival in advanced thyroid cancer. Endocr Relat Cancer 15:1069–1074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Zhu XD, Zhang JB, Zhuang PY, Zhu HG, Zhang W, Xiong YQ, Wu WZ, Wang L, Tang ZY, Sun HC (2008) High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol 26:2707–2716

    Article  PubMed  Google Scholar 

  19. Farinha P, Masoudi H, Skinnider BF, Shumansky K, Spinelli JJ, Gill K, Klasa R, Voss N, Connors JM, Gascoyne RD (2005) Analysis of multiple biomarkers shows that lymphoma-associated macrophage (LAM) content is an independent predictor of survival in follicular lymphoma (FL). Blood 106:2169–2174

    Article  CAS  PubMed  Google Scholar 

  20. Ojalvo LS, King W, Cox D, Pollard JW (2009) High-density gene expression analysis of tumor-associated macrophages from mouse mammary tumors. Am J Pathol 174:1048–1064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zabuawala T, Taffany DA, Sharma SM, Merchant A, Adair B, Srinivasan R, Rosol TJ, Fernandez S, Huang K, Leone G, Ostrowski MC (2010) An ets2-driven transcriptional program in tumor-associated macrophages promotes tumor metastasis. Cancer Res 70:1323–1333

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Groblewska M, Mroczko B, Wereszczynska-Siemiatkowska U, Mysliwiec P, Kedra B, Szmitkowski M (2007) Serum levels of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF) in pancreatic cancer patients. Clin Chem Lab Med 45:30–34

    Article  CAS  PubMed  Google Scholar 

  23. Lin EY, Gouon-Evans V, Nguyen AV, Pollard JW (2002) The macrophage growth factor CSF-1 in mammary gland development and tumor progression. J Mammary Gland Biol Neoplasia 7:147–162

    Article  PubMed  Google Scholar 

  24. Mantovani A, Sica A (2010) Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol 22:231–237

    Article  CAS  PubMed  Google Scholar 

  25. Mroczko B, Groblewska M, Wereszczynska-Siemiatkowska U, Okulczyk B, Kedra B, Laszewicz W, Dabrowski A, Szmitkowski M (2007) Serum macrophage-colony stimulating factor levels in colorectal cancer patients correlate with lymph node metastasis and poor prognosis. Clin Chim Acta 380:208–212

    Article  CAS  PubMed  Google Scholar 

  26. Sapi E, Kacinski BM (1999) The role of CSF-1 in normal and neoplastic breast physiology. Proc Soc Exp Biol Med 220:1–8

    CAS  PubMed  Google Scholar 

  27. Smith HO, Anderson PS, Kuo DY, Goldberg GL, DeVictoria CL, Boocock CA, Jones JG, Runowicz CD, Stanley ER, Pollard JW (1995) The role of colony-stimulating factor 1 and its receptor in the etiopathogenesis of endometrial adenocarcinoma. Clin Cancer Res 1:313–325

    CAS  PubMed  Google Scholar 

  28. Bailey C, Negus R, Morris A, Ziprin P, Goldin R, Allavena P, Peck D, Darzi A (2007) Chemokine expression is associated with the accumulation of tumour associated macrophages (TAMs) and progression in human colorectal cancer. Clin Exp Metastasis 24:121–130

    Article  CAS  PubMed  Google Scholar 

  29. Saji H, Koike M, Yamori T, Saji S, Seiki M, Matsushima K, Toi M (2001) Significant correlation of monocyte chemoattractant protein-1 expression with neovascularization and progression of breast carcinoma. Cancer 92:1085–1091

    Article  CAS  PubMed  Google Scholar 

  30. Tanaka K, Kurebayashi J, Sohda M, Nomura T, Prabhakar U, Yan L, Sonoo H (2009) The expression of monocyte chemotactic protein-1 in papillary thyroid carcinoma is correlated with lymph node metastasis and tumor recurrence. Thyroid 19:21–25

    Article  CAS  PubMed  Google Scholar 

  31. Yoshidome H, Kohno H, Shida T, Kimura F, Shimizu H, Ohtsuka M, Nakatani Y, Miyazaki M (2009) Significance of monocyte chemoattractant protein-1 in angiogenesis and survival in colorectal liver metastases. Int J Oncol 34:923–930

    Article  CAS  PubMed  Google Scholar 

  32. Zijlmans HJ, Fleuren GJ, Baelde HJ, Eilers PH, Kenter GG, Gorter A (2006) The absence of CCL2 expression in cervical carcinoma is associated with increased survival and loss of heterozygosity at 17q11.2. J Pathol 208:507–517

    Article  CAS  PubMed  Google Scholar 

  33. Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K, Shibuya M, Saya H, Suda T (2009) M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J Exp Med 206:1089–1102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Oguma K, Oshima H, Aoki M, Uchio R, Naka K, Nakamura S, Hirao A, Saya H, Taketo MM, Oshima M (2008) Activated macrophages promote Wnt signalling through tumour necrosis factor-alpha in gastric tumour cells. EMBO J 27:1671–1681

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Abraham D, Zins K, Sioud M, Lucas T, Schafer R, Stanley ER, Aharinejad S (2010) Stromal cell-derived CSF-1 blockade prolongs xenograft survival of CSF-1-negative neuroblastoma. Int J Cancer 126:1339–1352

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Aharinejad S, Sioud M, Lucas T, Abraham D (2009) Targeting stromal-cancer cell interactions with siRNAs. Methods Mol Biol 487:243–266

    CAS  PubMed  Google Scholar 

  37. Ghezzi P et al (1991) Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. Cytokine 3:189–194

    Article  CAS  PubMed  Google Scholar 

  38. Scannell G et al (1993) Hypoxia induces a human macrophage cell line to release tumor necrosis factor-alpha and its soluble receptors in vitro. J Surg Res 54:281–285. https://doi.org/10.1006/jsre.1993.1044

    Article  CAS  PubMed  Google Scholar 

  39. Yun JK et al (1997) Inflammatory mediators are perpetuated in macrophages resistant to apoptosis induced by hypoxia. Proc Natl Acad Sci USA 94:13903–13908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Scannell G et al (1995) Effects of trauma on leukocyte intercellular adhesion molecule-1, CD11b, and CD18 expressions. J Trauma 39:641–644

    Article  CAS  PubMed  Google Scholar 

  41. Acosta JC et al (2013) A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 15:978–990. https://doi.org/10.1038/ncb2784

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Leeper-Woodford SK, Mills JW (1992) Phagocytosis and ATP levels in alveolar macrophages during acute hypoxia. Am J Respir Cell Mol Biol 6:326–334. https://doi.org/10.1165/ajrcmb/6.3.326

    Article  CAS  PubMed  Google Scholar 

  43. Clever D, Roychoudhuri R, Constantinides MG, Askenase MH, Sukumar M, Klebanoff CA, Eil RL, Hickman HD, Yu Z, Pan JH, Palmer DC, Phan AT, Goulding J, Gattinoni L, Goldrath AW, Belkaid Y, Restifo NP (2016) Oxygen sensing by T cells establishes an immunologically tolerant metastatic niche. Cell 166:1117–1131. e1114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Hiratsuka S, Goel S, Kamoun WS, Maru Y, Fukumura D, Duda DG, Jain RK (2011) Endothelial focal adhesion kinase mediates cancer cell homing to discrete regions of the lungs via E-selectin up-regulation. Proc Natl Acad Sci USA 108:3725–3730

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Hiratsuka S, Ishibashi S, Tomita T, Watanabe A, Akashi-Takamura S, Murakami M, Kijima H, Miyake K, Aburatani H, Maru Y (2013) Primary tumours modulate innate immune signalling to create pre-metastatic vascular hyperpermeability foci. Nat Commun 4:1853

    Article  PubMed  Google Scholar 

  46. Hiratsuka S, Tomita T, Mishima T, Matsunaga Y, Omori T, Ishibashi S, Yamaguchi S, Hosogane T, Watarai H, Omori-Miyake M, Yamamoto T, Shibata N, Watanabe A, Aburatani H, Tomura M, High KA, Maru Y (2018) Hepato-entrained B220(+)CD11c(+)NK1.1(+) cells regulate pre-metastatic niche formation in the lung. EMBO Mol Med 10

    Google Scholar 

  47. Baay-Guzman GJ et al (2012) HIF-1 expression is associated with CCL2 chemokine expression in airway inflammatory cells: implications in allergic airway inflammation. Respir Res 13:60. https://doi.org/10.1186/1465-9921-13-60

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Padua D, Zhang XH, Wang Q, Nadal C, Gerald WL, Gomis RR, Massague J (2008) TGFbeta primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133:66–77

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhang H, Wong CCL, Wei H, Gilkes DM, Korangath P, Chaturvedi P, Schito L, Chen J, Krishnamachary B, Winnard PT, Raman V, Zhen L, Mitzner WA, Sukumar S, Semenza GL (2012) HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs. Oncogene 31:1757–1770

    Article  CAS  PubMed  Google Scholar 

  50. Hiratsuka S, Watanabe A, Aburatani H, Maru Y (2006) Tumour-mediated upregulation of chemoattractants and recruitment of myeloid cells predetermines lung metastasis. Nat Cell Biol 8:1369–1375

    Article  CAS  PubMed  Google Scholar 

  51. Hiratsuka S, Watanabe A, Sakurai Y, Akashi-Takamura S, Ishibashi S, Miyake K, Shibuya M, Akira S, Aburatani H, Maru Y (2008) The S100A8-serum amyloid A3-TLR4 paracrine cascade establishes a pre-metastatic phase. Nat Cell Biol 10:1349–1355

    Article  CAS  PubMed  Google Scholar 

  52. Grebhardt S, Veltkamp C, Strobel P, Mayer D (2012) Hypoxia and HIF-1 increase S100A8 and S100A9 expression in prostate cancer. Int J Cancer 131:2785–2794. https://doi.org/10.1002/ijc.27591

    Article  CAS  PubMed  Google Scholar 

  53. Hiratsuka S, Nakamura K, Iwai S, Murakami M, Itoh T, Kijima H, Shipley JM, Senior RM, Shibuya M (2002) MMP9 induction by vascular endothelial growth factor receptor-1 is involved in lung-specific metastasis. Cancer Cell 2:289–300

    Article  CAS  PubMed  Google Scholar 

  54. Shan Y et al (2018) Hypoxia-induced matrix metalloproteinase-13 expression in exosomes from nasopharyngeal carcinoma enhances metastases. Cell Death Dis 9:382. https://doi.org/10.1038/s41419-018-0425-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nannuru KC et al (2010) Matrix metalloproteinase (MMP)-13 regulates mammary tumor-induced osteolysis by activating MMP9 and transforming growth factor-beta signaling at the tumor-bone interface. Cancer Res 70:3494–3504. https://doi.org/10.1158/0008-5472.CAN-09-3251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wong CC, Tse AP, Huang YP, Zhu YT, Chiu DK, Lai RK, Au SL, Kai AK, Lee JM, Wei LL, Tsang FH, Lo RC, Shi J, Zheng YP, Wong CM, Ng IO (2014) Lysyl oxidase-like 2 is critical to tumor microenvironment and metastatic niche formation in hepatocellular carcinoma. Hepatology 60:1645–1658

    Article  CAS  PubMed  Google Scholar 

  57. Levental KR, Yu H, Kass L, Lakins JN, Egeblad M, Erler JT, Fong SF, Csiszar K, Giaccia A, Weninger W, Yamauchi M, Gasser DL, Weaver VM (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139:891–906

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Wong CC, Gilkes DM, Zhang H, Chen J, Wei H, Chaturvedi P, Fraley SI, Wong CM, Khoo US, Ng IO, Wirtz D, Semenza GL (2011) Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci USA 108:16369–16374

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Barry-Hamilton V, Spangler R, Marshall D, McCauley S, Rodriguez HM, Oyasu M, Mikels A, Vaysberg M, Ghermazien H, Wai C, Garcia CA, Velayo AC, Jorgensen B, Biermann D, Tsai D, Green J, Zaffryar-Eilot S, Holzer A, Ogg S, Thai D, Neufeld G, Van Vlasselaer P, Smith V (2010) Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 16:1009–1017

    Article  CAS  PubMed  Google Scholar 

  60. Wong CC, Zhang H, Gilkes DM, Chen J, Wei H, Chaturvedi P, Hubbi ME, Semenza GL (2012) Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis. J Mol Med (Berl) 90:803–815

    Article  CAS  Google Scholar 

  61. Cox TR, Rumney RMH, Schoof EM, Perryman L, Hoye AM, Agrawal A, Bird D, Latif NA, Forrest H, Evans HR, Huggins ID, Lang G, Linding R, Gartland A, Erler JT (2015) The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase. Nature 522:106–110

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Qian BZ, Li J, Zhang H, Kitamura T, Zhang J, Campion LR, Kaiser EA, Snyder LA, Pollard JW (2011) CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis. Nature 475:222–225

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. McAllister SS, Gifford AM, Greiner AL, Kelleher SP, Saelzler MP, Ince TA, Reinhardt F, Harris LN, Hylander BL, Repasky EA, Weinberg RA (2008) Systemic endocrine instigation of indolent tumor growth requires osteopontin. Cell 133:994–1005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kelly T, Suva LJ, Huang Y, Macleod V, Miao HQ, Walker RC, Sanderson RD (2005) Expression of heparanase by primary breast tumors promotes bone resorption in the absence of detectable bone metastases. Cancer Res 65:5778–5784

    Article  CAS  PubMed  Google Scholar 

  65. Guise TA, Yin JJ, Taylor SD, Kumagai Y, Dallas M, Boyce BF, Yoneda T, Mundy GR (1996) Evidence for a causal role of parathyroid hormone-related protein in the pathogenesis of human breast cancer-mediated osteolysis. J Clin Invest 98:1544–1549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Korpal M, Yan J, Lu X, Xu S, Lerit DA, Kang Y (2009) Imaging transforming growth factor-beta signaling dynamics and therapeutic response in breast cancer bone metastasis. Nat Med 15:960–966

    Article  CAS  PubMed  Google Scholar 

  67. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3:537–549

    Article  CAS  PubMed  Google Scholar 

  68. Liang Z, Wu T, Lou H, Yu X, Taichman RS, Lau SK, Nie S, Umbreit J, Shim H (2004) Inhibition of breast cancer metastasis by selective synthetic polypeptide against CXCR4. Cancer Res 64:4302–4308

    Article  CAS  PubMed  Google Scholar 

  69. Lu X, Wang Q, Hu G, Van Poznak C, Fleisher M, Reiss M, Massague J, Kang Y (2009) ADAMTS1 and MMP1 proteolytically engage EGF-like ligands in an osteolytic signaling cascade for bone metastasis. Genes Dev 23:1882–1894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Tang ZN, Zhang F, Tang P, Qi XW, Jiang J (2011) Hypoxia induces RANK and RANKL expression by activating HIF-1alpha in breast cancer cells. Biochem Biophys Res Commun 408:411–416. https://doi.org/10.1016/j.bbrc.2011.04.035

    Article  CAS  PubMed  Google Scholar 

  71. Manisterski M, Golan M, Amir S, Weisman Y, Mabjeesh NJ (2010) Hypoxia induces PTHrP gene transcription in human cancer cells through the HIF-2alpha. Cell Cycle 9:3723–3729

    Article  CAS  PubMed  Google Scholar 

  72. Sethi N, Dai X, Winter CG, Kang Y (2011) Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19:192–205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Zheng H, Bae Y, Kasimir-Bauer S, Tang R, Chen J, Ren G, Yuan M, Esposito M, Li W, Wei Y, Shen M, Zhang L, Tupitsyn N, Pantel K, King C, Sun J, Moriguchi J, Jun HT, Coxon A, Lee B, Kang Y (2017) Therapeutic antibody targeting tumor- and osteoblastic niche-derived Jagged1 sensitizes bone metastasis to chemotherapy. Cancer Cell 32(731–747):e736

    Google Scholar 

  74. Park JE et al (2010) Hypoxic tumor cell modulates its microenvironment to enhance angiogenic and metastatic potential by secretion of proteins and exosomes. Mol Cell Proteomics 9:1085–1099. https://doi.org/10.1074/mcp.M900381-MCP200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Peinado H, Aleckovic M, Lavotshkin S, Matei I, Costa-Silva B, Moreno-Bueno G, Hergueta-Redondo M, Williams C, Garcia-Santos G, Ghajar C, Nitadori-Hoshino A, Hoffman C, Badal K, Garcia BA, Callahan MK, Yuan J, Martins VR, Skog J, Kaplan RN, Brady MS, Wolchok JD, Chapman PB, Kang Y, Bromberg J, Lyden D (2012) Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat Med 18:883–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Kucharzewska P et al (2013) Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development. Proc Natl Acad Sci USA 110:7312–7317. https://doi.org/10.1073/pnas.1220998110

    Article  PubMed  PubMed Central  Google Scholar 

  77. Costa-Silva B, Aiello NM, Ocean AJ, Singh S, Zhang H, Thakur BK, Becker A, Hoshino A, Mark MT, Molina H, Xiang J, Zhang T, Theilen TM, Garcia-Santos G, Williams C, Ararso Y, Huang Y, Rodrigues G, Shen TL, Labori KJ, Lothe IM, Kure EH, Hernandez J, Doussot A, Ebbesen SH, Grandgenett PM, Hollingsworth MA, Jain M, Mallya K, Batra SK, Jarnagin WR, Schwartz RE, Matei I, Peinado H, Stanger BZ, Bromberg J, Lyden D (2015) Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol 17:816–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Hoshino A, Costa-Silva B, Shen TL, Rodrigues G, Hashimoto A, Tesic Mark M, Molina H, Kohsaka S, Di Giannatale A, Ceder S, Singh S, Williams C, Soplop N, Uryu K, Pharmer L, King T, Bojmar L, Davies AE, Ararso Y, Zhang T, Zhang H, Hernandez J, Weiss JM, Dumont-Cole VD, Kramer K, Wexler LH, Narendran A, Schwartz GK, Healey JH, Sandstrom P, Labori KJ, Kure EH, Grandgenett PM, Hollingsworth MA, de Sousa M, Kaur S, Jain M, Mallya K, Batra SK, Jarnagin WR, Brady MS, Fodstad O, Muller V, Pantel K, Minn AJ, Bissell MJ, Garcia BA, Kang Y, Rajasekhar VK, Ghajar CM, Matei I, Peinado H, Bromberg J, Lyden D (2015) Tumour exosome integrins determine organotropic metastasis. Nature 527:329–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Plebanek MP, Angeloni NL, Vinokour E, Li J, Henkin A, Martinez-Marin D, Filleur S, Bhowmick R, Henkin J, Miller SD, Ifergan I, Lee Y, Osman I, Thaxton CS, Volpert OV (2017) Pre-metastatic cancer exosomes induce immune surveillance by patrolling monocytes at the metastatic niche. Nat Commun 8:1319

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. Authors Cerise Yuen-Ki Chan and Vincent Wai-Hin Yuen have equally contributed to this chapter.

Authors and Affiliations

  1. Department of Pathology, The University of Hong Kong, Pokfulam, Hong Kong

    Cerise Yuen-Ki Chan, Vincent Wai-Hin Yuen & Carmen Chak-Lui Wong

Authors
  1. Cerise Yuen-Ki Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vincent Wai-Hin Yuen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carmen Chak-Lui Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Carmen Chak-Lui Wong .

Editor information

Editors and Affiliations

  1. Breast and Ovarian Cancer Program, Department of Oncology, The Johns Hopkins School of Medicine, Baltimore, MD, USA

    Daniele M. Gilkes

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chan, C.YK., Yuen, V.WH., Wong, C.CL. (2019). Hypoxia and the Metastatic Niche. In: Gilkes, D. (eds) Hypoxia and Cancer Metastasis. Advances in Experimental Medicine and Biology, vol 1136. Springer, Cham. https://doi.org/10.1007/978-3-030-12734-3_7

Download citation

Publish with us

Policies and ethics

Search

Navigation