Abstract
Secreted Protein Acidic and Rich in Cysteine (SPARC) is a matricellular protein that modulates the levels of cell adhesion and migration, as well as regulates cell proliferation, survival, and angiogenesis during normal development and tissue remodeling. These same cellular processes are necessary for tumor growth and progression, and they proceed as a result of the interplay between the tumor cells and the stromal and immune cells within the tissue microenvironment. Evidence suggests that SPARC contributes to these tumor-associated processes; however, deciphering its role is complicated by the fact that SPARC may be produced and secreted by cancer cells, stromal cells, and immune cells resulting in autocrine and paracrine effects on the tumor microenvironment. Its ability to promote deadhesion of cells from the ECM results in tumor and stromal cell migration and dissemination. It can also inhibit proliferation in cancer cells, fibroblasts, and endothelial cells directly or indirectly by binding to various growth factors and inhibiting downstream signaling. In addition, SPARC can regulate ECM deposition, assembly, and remodeling by regulating collagen processing and altering the secretion of matrix proteins and matrix degrading proteases from cancer cells and stromal cells. Finally, SPARC can also regulate the tumor microenvironment by suppressing immune cell infiltration and limiting tumor elimination. The evidence for each of these functions of SPARC in the regulation of the tumor microenvironment will be discussed.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- AML:
-
acute myeloid leukemia
- BAE:
-
bovine aortic endothelial
- bFGF:
-
basic fibroblast growth factor
- CAM assay:
-
chorioallantoic membrane assay
- cDNA:
-
complementary DNA
- CHS:
-
cutaneous contact hypersensitivity
- CN:
-
collagen
- CRAd:
-
conditionally replicative oncolytic adenovirus
- EC:
-
extracellular
- ECM:
-
extracellular matrix
- EGF-like:
-
epidermal growth factor-like
- EMT:
-
epithelial-mesenchymal transition
- F:
-
fibroblasts
- FAK:
-
focal adhesion kinase
- FN:
-
fibronectin
- HA:
-
hyaluronic acid
- HSP27:
-
heat shock protein 27
- IL-6:
-
interleukin-6
- ILK:
-
integrin-linked kinase
- ip:
-
intraperitoneal
- iv:
-
intravenous
- L:
-
leukocytes
- LN:
-
laminin
- LPA:
-
lysophosphatidic acid
- LPS:
-
lipopolysaccharide
- M:
-
methylated
- MCP-1:
-
monocyte chemoattractant protein
- ME:
-
methylation
- mets:
-
metastases
- MLL gene:
-
mixed lineage leukemia gene
- MMP(s):
-
matrix metalloproteinase(s)
- Mo:
-
macrophages
- mRNA:
-
messenger RNA
- MT1-MMP:
-
membrane type 1- matrix metalloproteinase
- MVD:
-
microvascular density
- N:
-
neutrophils
- NC:
-
no change
- NF-kappaB:
-
nuclear factor kappaB
- P:
-
pericytes
- p38 MAPK:
-
p38 mitogen activated protein kinase
- PDGF:
-
platelet-derived growth factor
- PGE2:
-
prostaglandin E2
- PMN(s):
-
polymorphonuclear leukocyte(s)
- [R]:
-
VEGF receptor
- sc:
-
subcutaneous
- shRNA:
-
short hairpin RNA
- siRNA:
-
short interfering RNA
- SPARC:
-
secreted protein acidic and rich in cysteine
- TGF-beta:
-
transforming growth factor-beta
- THR:
-
T/tAg, hTERT, H-rasV12G
- TIMP:
-
tissue inhibitor of metalloproteinase
- TRAMP:
-
transgenic adenocarcinoma of mouse prostate
- U:
-
unmethylated
- uPA:
-
urokinase plasminogen activator
- uPAR:
-
uPA receptor
- VN:
-
vitronectin
- VEGF:
-
vascular endothelial growth factor
- wt:
-
wild-type
References
Alonso SR, Tracey L et al (2007) A high-throughput study in melanoma identifies epithelial-mesenchymal transition as a major determinant of metastasis. Cancer Res 67(7):3450–3460
Alvarez MJ, Prada F et al (2005) Secreted protein acidic and rich in cysteine produced by human melanoma cells modulates polymorphonuclear leukocyte recruitment and antitumor cytotoxic capacity. Cancer Res 65(12):5123–5132
Amatschek S, Koenig U et al (2004) Tissue-wide expression profiling using cDNA subtraction and microarrays to identify tumor-specific genes. Cancer Res 64(3):844–856
Arnold S, Mira E et al (2008) Forced expression of MMP9 rescues the loss of angiogenesis and abrogates metastasis of pancreatic tumors triggered by the absence of host SPARC. Exp Biol Med 233(7):860–873
Aycock RL, Bradshaw AC et al (2004) Development of UV-induced squamous cell carcinomas is suppressed in the absence of SPARC. J Invest Dermatol 123(3):592–599
Barker TH, Baneyx G et al (2005) SPARC regulates extracellular matrix organization through its modulation of integrin-linked kinase activity. J Biol Chem 280(43):36483–36493
Barth PJ, Moll R et al (2005) Stromal remodeling and SPARC (secreted protein acid rich in cysteine) expression in invasive ductal carcinomas of the breast. Virchows Arch 446(5):532–536
Beck AH, Espinosa I et al (2008) The fibromatosis signature defines a robust stromal response in breast carcinoma. Lab Invest 88(6):591–601
Bergamaschi A, Tagliabue E et al (2008). Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol 214(3):357–367
Bornstein P, Sage EH (2002) Matricellular proteins: extracellular modulators of cell function. Curr Opin Cell Biol 14(5):608–616
Bozkurt SU, Ayan E et al (2009) Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomas. APMIS 117(9):651–659
Bradshaw AD, Francki A et al (1999) Primary mesenchymal cells isolated from SPARC-null mice exhibit altered morphology and rates of proliferation. Mol Biol Cell 10(5):1569–1579
Brekken RA, Sage EH (2001) SPARC, a matricellular protein: at the crossroads of cell-matrix communication. Matrix Biol 19(8):816–827
Brekken RA, Puolakkainen P et al (2003) Enhanced growth of tumors in SPARC null mice is associated with changes in the ECM. J Clin Invest 111(4):487–495
Brown TJ, Shaw PA et al (1999) Activation of SPARC expression in reactive stroma associated with human epithelial ovarian cancer. Gynecol Oncol 75(1):25–33
Brune K, Hong SM et al (2008) Genetic and epigenetic alterations of familial pancreatic cancers. Cancer Epidemiol Biomark Prev 17(12):3536–3542
Bull Phelps SL, Carbon J et al (2009) Secreted protein acidic and rich in cysteine as a regulator of murine ovarian cancer growth and chemosensitivity. Am J Obstet Gynecol 200(2):180 e1–e7
Chan SK, Griffith OL et al (2008) Meta-analysis of colorectal cancer gene expression profiling studies identifies consistently reported candidate biomarkers. Cancer Epidemiol Biomark Prev 17(3):543–552
Che Y, Luo A et al (2006) The differential expression of SPARC in esophageal squamous cell carcinoma. Int J Mol Med 17(6):1027–1033
Cheetham S, Tang MJ et al (2008) SPARC promoter hypermethylation in colorectal cancers can be reversed by 5-Aza-2′deoxycytidine to increase SPARC expression and improve therapy response. Br J Cancer 98(11):1810–1819
Chin D, Boyle GM et al (2005). Novel markers for poor prognosis in head and neck cancer. Int J Cancer 113(5):789–797
Chlenski A, Liu S et al (2002) SPARC is a key Schwannian-derived inhibitor controlling neuroblastoma tumor angiogenesis. Cancer Res 62(24):7357–7363
Chlenski A, Liu S et al (2004) Neuroblastoma angiogenesis is inhibited with a folded synthetic molecule corresponding to the epidermal growth factor-like module of the follistatin domain of SPARC. Cancer Res 64(20):7420–7425
Chlenski A, Liu S et al (2006) SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix. Int J Cancer 118(2):310–316
Chlenski A, Guerrero LJ et al (2007) SPARC enhances tumor stroma formation and prevents fibroblast activation. Oncogene 26(31):4513–4522
Colombo MP, Ferrari G et al (1991) Down-regulation of SPARC/osteonectin/BM-40 expression in methylcholanthrene-induced fibrosarcomas and in Kirsten-MSV transformed fibroblasts. Eur J Cancer 27(1):58–62
Dalla-Torre CA, Yoshimoto M et al (2006) Effects of THBS3, SPARC and SPP1 expression on biological behavior and survival in patients with osteosarcoma. BMC Cancer 6:237
De Craene B, van Roy F et al (2005) Unraveling signalling cascades for the Snail family of transcription factors. Cell Signal 17(5):535–547
Desai N, Trieu V et al (2009) SPAR+C Expression correlates with tumor response to albumin-bound paclitaxel in head and neck cancer patients. Transl Oncol 2(2):59–64
DiMartino JF, Lacayo NJ et al (2006) Low or absent SPARC expression in acute myeloid leukemia with MLL rearrangements is associated with sensitivity to growth inhibition by exogenous SPARC protein. Leukemia 20(3):426–432
Funk SE, Sage EH (1991) The Ca2(+)-binding glycoprotein SPARC modulates cell cycle progression in bovine aortic endothelial cells. Proc Natl Acad Sci U S A 88(7):2648–2652
Gagliano N, Moscheni C et al (2006) Effect of Ukrain on matrix metalloproteinase-2 and Secreted Protein Acidic and Rich in Cysteine (SPARC) expression in human glioblastoma cells. Anticancer Drugs 17(2):189–194
Gieseg MA, Cody T et al (2002) Expression profiling of human renal carcinomas with functional taxonomic analysis. BMC Bioinforma 3:26
Golembieski WA, Ge S et al (1999) Increased SPARC expression promotes U87 glioblastoma invasion in vitro. Int J Dev Neurosci 17(5–6):463–472
Golembieski WA, Thomas SL et al (2008) HSP27 mediates SPARC-induced changes in glioma morphology, migration, and invasion. Glia 56(10):1061–1075
Gurion R, Vidal L et al (2009) 5-azacitidine prolongs overall survival in patients with myelodysplastic syndrome – systematic review and meta-analysis. Haematologica 2009 Sep 22 [Epub ahead of print]
Haber CL, Gottifredi V et al (2008) SPARC modulates the proliferation of stromal but not melanoma cells unless endogenous SPARC expression is downregulated. Int J Cancer 122(7):1465–1475
Hecht JT, Sage EH (2006) Retention of the matricellular protein SPARC in the endoplasmic reticulum of chondrocytes from patients with pseudoachondroplasia. J Histochem Cytochem 54(3):269–274
Heller G, Schmidt WM et al (2008) Genome-wide transcriptional response to 5-aza-2′-deoxycytidine and trichostatin a in multiple myeloma cells. Cancer Res 68(1):44–54
Hong SM, Kelly D et al (2008) Multiple genes are hypermethylated in intraductal papillary mucinous neoplasms of the pancreas. Mod Pathol 21(12):1499–1507
Huynh MH, Hong H et al (2000) Association of SPARC (osteonectin, BM-40) with extracellular and intracellular components of the ciliated surface ectoderm of Xenopus embryos. Cell Motil Cytoskeleton 47(2):154–162
Ikuta Y, Hayashida Y et al (2009) Identification of the H2-Kd-restricted cytotoxic T lymphocyte epitopes of a tumor-associated antigen, SPARC, which can stimulate antitumor immunity without causing autoimmune disease in mice. Cancer Sci 100(1):132–137
Infante JR, Matsubayashi H et al (2007) Peritumoral fibroblast SPARC expression and patient outcome with resectable pancreatic adenocarcinoma. J Clin Oncol 25(3):319–325
Jones C, Mackay A et al (2004) Expression profiling of purified normal human luminal and myoepithelial breast cells: identification of novel prognostic markers for breast cancer. Cancer Res 64(9):3037–3045
Junnila S, Kokkola A et al (2009) Gene expression analysis identifies over-expression of CXCL1, SPARC, SPP1, and SULF1 in gastric cancer. Genes Chromosomes Cancer 2009 Sep 24. [Epub ahead of print]
Kamihagi K, Katayama M et al (1994) Osteonectin/SPARC regulates cellular secretion rates of fibronectin and laminin extracellular matrix proteins. Biochem Biophys Res Commun 200(1):423–428
Kato Y, Nagashima Y et al (2005) Expression of SPARC in tongue carcinoma of stage II is associated with poor prognosis: an immunohistochemical study of 86 cases. Int J Mol Med 16(2):263–268
Kelly KA, Allport JR et al (2007) SPARC is a VCAM-1 counter-ligand that mediates leukocyte transmigration. J Leukoc Biol 81(3):748–756
Koblinski JE, Kaplan-Singer BR et al (2005) Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis. Cancer Res 65(16):7370–7377
Koukourakis MI, Giatromanolaki A et al (2003) Enhanced expression of SPARC/osteonectin in the tumor-associated stroma of non-small cell lung cancer is correlated with markers of hypoxia/acidity and with poor prognosis of patients. Cancer Res 63(17):5376–5380
Kraemer M, Tournaire R et al (1999) Rat embryo fibroblasts transformed by c-Jun display highly metastatic and angiogenic activities in vivo and deregulate gene expression of both angiogenic and antiangiogenic factors. Cell Growth Differ 10(3):193–200
Kunigal S, Gondi CS et al (2006) SPARC-induced migration of glioblastoma cell lines via uPA-uPAR signaling and activation of small GTPase RhoA. Int J Oncol 29(6):1349–1357
Kupprion C, Motamed K et al (1998) SPARC (BM-40, osteonectin) inhibits the mitogenic effect of vascular endothelial growth factor on microvascular endothelial cells. J Biol Chem 273(45):29635–29640
Kzhyshkowska J, Workman G et al (2006) Novel function of alternatively activated macrophages: stabilin-1-mediated clearance of SPARC. J Immunol 176(10):5825–5832
Lane TF, Iruela-Arispe ML et al (1992) Regulation of gene expression by SPARC during angiogenesis in vitro. Changes in fibronectin, thrombospondin-1, and plasminogen activator inhibitor-1. J Biol Chem 267(23):16736–16745
Lapointe J, Li C et al (2004) Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci U S A 101(3):811–816
Lau CP, Poon RT et al (2006) SPARC and Hevin expression correlate with tumour angiogenesis in hepatocellular carcinoma. J Pathol 210(4):459–468
Le Bail B, Faouzi S et al (1999) Osteonectin/SPARC is overexpressed in human hepatocellular carcinoma. J Pathol 189(1):46–52
Ledda MF, Bravo AI et al (1997a) The expression of the secreted protein acidic and rich in cysteine (SPARC) is associated with the neoplastic progression of human melanoma. J Invest Dermatol 108(2):210–214
Ledda MF, Adris S et al (1997b) Suppression of SPARC expression by antisense RNA abrogates the tumorigenicity of human melanoma cells. Nat Med 3(2):171–176
Lopez MV, Blanco P et al (2006) Expression of a suicidal gene under control of the human secreted protein acidic and rich in cysteine (SPARC) promoter in tumor or stromal cells led to the inhibition of tumor cell growth. Mol Cancer Ther 5(10):2503–2511
Lopez MV, Viale DL et al (2009) Tumor associated stromal cells play a critical role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses. PLoS One 4(4):e5119
Luo A, Kong J et al (2004) Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene 23(6):1291–1299
Maloney SC, Marshall JC et al (2009) SPARC is expressed in human uveal melanoma and its abrogation reduces tumor cell proliferation. Anticancer Res 29(8):3059–3064
Mann K, Deutzmann R et al (1987) Solubilization of protein BM-40 from a basement membrane tumor with chelating agents and evidence for its identity with osteonectin and SPARC. FEBS Lett 218(1):167–172
McClung HM, Thomas SL et al (2007) SPARC upregulates MT1-MMP expression, MMP-2 activation, and the secretion and cleavage of galectin-3 in U87MG glioma cells. Neurosci Lett 419(2):172–177
Mok SC, Chan WY et al (1996) SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells. Oncogene 12(9):1895–1901
Motamed K, Blake DJ (2003) Fibroblast growth factor receptor-1 mediates the inhibition of endothelial cell proliferation and the promotion of skeletal myoblast differentiation by SPARC: a role for protein kinase A. J Cell Biochem 90(2):408–423
Motamed K, Sage EH (1998) SPARC inhibits endothelial cell adhesion but not proliferation through a tyrosine phosphorylation-dependent pathway. J Cell Biochem 70(4):543–552
Paley PJ, Goff BA et al (2000) Alterations in SPARC and VEGF immunoreactivity in epithelial ovarian cancer. Gynecol Oncol 78(3 Pt 1):336–341
Pan MR, Chang HC et al (2008) The nonsteroidal anti-inflammatory drug NS398 reactivates SPARC expression via promoter demethylation to attenuate invasiveness of lung cancer cells. Exp Biol Med (Maywood) 233(4):456–462
Pen A, Moreno MJ et al (2007) Molecular markers of extracellular matrix remodeling in glioblastoma vessels: microarray study of laser-captured glioblastoma vessels. Glia 55(6):559–572
Porter D, Lahti-Domenici J et al (2003) Molecular markers in ductal carcinoma in situ of the breast. Mol Cancer Res 1(5):362–375
Prada F, Benedetti LG et al (2007) SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth. J Invest Dermatol 127(11):2618–2628
Puolakkainen PA, Brekken RA et al (2004) Enhanced growth of pancreatic tumors in SPARC-null mice is associated with decreased deposition of extracellular matrix and reduced tumor cell apoptosis. Mol Cancer Res 2(4):215–224
Raines EW, Lane TF et al (1992) The extracellular glycoprotein SPARC interacts with platelet-derived growth factor (PDGF)-AB and -BB and inhibits the binding of PDGF to its receptors. Proc Natl Acad Sci U S A 89(4):1281–1285
Rempel SA, Ge S et al (1999) SPARC: a potential diagnostic marker of invasive meningiomas. Clin Cancer Res 5(2):237–241
Rempel SA, Golembieski WA et al (1998) SPARC: a signal of astrocytic neoplastic transformation and reactive response in human primary and xenograft gliomas. J Neuropathol Exp Neurol 57(12):1112–1121
Rempel SA, Golembieski WA et al (2001) SPARC modulates cell growth, attachment and migration of U87 glioma cells on brain extracellular matrix proteins. J Neurooncol 53(2):149–160
Rempel SA, Hawley RC et al (2007) Splenic and immune alterations of the Sparc-null mouse accompany a lack of immune response. Genes Immun 8(3):262–274
Rentz TJ, Poobalarahi F et al (2007) SPARC regulates processing of procollagen I and collagen fibrillogenesis in dermal fibroblasts. J Biol Chem 282(30):22062–22071
Rich JN, Shi Q et al (2003) Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model. J Biol Chem 278(18):15951–15957
Rich JN, Hans C et al (2005) Gene expression profiling and genetic markers in glioblastoma survival. Cancer Res 65(10):4051–4058
Rodriguez-Jimenez FJ, Caldes T et al (2007) Overexpression of SPARC protein contrasts with its transcriptional silencing by aberrant hypermethylation of SPARC CpG-rich region in endometrial carcinoma. Oncol Rep 17(6):1301–1307
Sage H, Johnson C et al (1984) Characterization of a novel serum albumin-binding glycoprotein secreted by endothelial cells in culture. J Biol Chem 259(6):3993–4007
Sage EH, Reed M et al (2003) Cleavage of the matricellular protein SPARC by matrix metalloproteinase 3 produces polypeptides that influence angiogenesis. J Biol Chem 278(39):37849–37857
Said N, Motamed K (2005) Absence of host-secreted protein acidic and rich in cysteine (SPARC) augments peritoneal ovarian carcinomatosis. Am J Pathol 167(6):1739–1752
Said N, Najwer I et al (2007a) Secreted protein acidic and rich in cysteine (SPARC) inhibits integrin-mediated adhesion and growth factor-dependent survival signaling in ovarian cancer. Am J Pathol 170(3):1054–1063
Said NA, Najwer I et al (2007b) SPARC inhibits LPA-mediated mesothelial-ovarian cancer cell crosstalk. Neoplasia 9(1):23–35
Said N, Socha MJ et al (2007c) Normalization of the ovarian cancer microenvironment by SPARC. Mol Cancer Res 5(10):1015–1030
Said NA, Elmarakby AA et al (2008). SPARC ameliorates ovarian cancer-associated inflammation. Neoplasia 10(10):1092–1104
Said N, Frierson HF Jr et al (2009) The role of SPARC in the TRAMP model of prostate carcinogenesis and progression. Oncogene 28(39):3487–3498
Sakai N, Baba M et al (2001) SPARC expression in primary human renal cell carcinoma: upregulation of SPARC in sarcomatoid renal carcinoma. Hum Pathol 32(10):1064–1070
Sangaletti S, Gioiosa L et al (2005) Accelerated dendritic-cell migration and T-cell priming in SPARC-deficient mice. J Cell Sci 118(Pt 16):3685–3694
Sangaletti S, Stoppacciaro A et al (2003) Leukocyte, rather than tumor-produced SPARC, determines stroma and collagen type IV deposition in mammary carcinoma. J Exp Med 198(10):1475–1485
Sangaletti S, Di Carlo E et al (2008) Macrophage-derived SPARC bridges tumor cell-extracellular matrix interactions toward metastasis. Cancer Res 68(21):9050–9059
Sansom OJ, Mansergh FC et al (2007) Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+mice. Gut 56(10):1410–1414
Sarrio D, Rodriguez-Pinilla SM et al (2008) Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res 68(4):989–997
Sato N, Fukushima N et al (2003) SPARC/osteonectin is a frequent target for aberrant methylation in pancreatic adenocarcinoma and a mediator of tumor-stromal interactions. Oncogene 22(32):5021–5030
Schittenhelm J, Mittelbronn M et al (2006) Patterns of SPARC expression and basement membrane intactness at the tumour-brain border of invasive meningiomas. Neuropathol Appl Neurobiol 32(5):525–531
Schultz C, Lemke N et al (2002) Secreted protein acidic and rich in cysteine promotes glioma invasion and delays tumor growth in vivo. Cancer Res 62(21):6270–6277
Seno T, Harada H et al (2009) Downregulation of SPARC expression inhibits cell migration and invasion in malignant gliomas. Int J Oncol 34(3):707–715
Shi Q, Bao S et al (2004) Secreted protein acidic, rich in cysteine (SPARC), mediates cellular survival of gliomas through AKT activation. J Biol Chem 279(50):52200–52209
Shi Q, Bao S et al (2007) Targeting SPARC expression decreases glioma cellular survival and invasion associated with reduced activities of FAK and ILK kinases. Oncogene 26(28):4084–4094
Smit DJ, Gardiner BB (2007) Osteonectin downregulates E-cadherin, induces osteopontin and focal adhesion kinase activity stimulating an invasive melanoma phenotype. Int J Cancer 121(12):2653–2660
Socha M, Said N et al (2009) Aberrant promoter methylation of SPARC in ovarian cancer. Neoplasia 11(2):126–135
Sosa MS, Girotti MR et al (2007) Proteomic analysis identified N-cadherin, clusterin, and HSP27 as mediators of SPARC (secreted protein, acidic and rich in cysteines) activity in melanoma cells. Proteomics 7(22):4123–4134
Suzuki M, Hao C et al (2005) Aberrant methylation of SPARC in human lung cancers. Br J Cancer 92(5):942–948
Taghizadeh F, Tang MJ et al (2007) Synergism between vitamin D and secreted protein acidic and rich in cysteine-induced apoptosis and growth inhibition results in increased susceptibility of therapy-resistant colorectal cancer cells to chemotherapy. Mol Cancer Ther 6(1):309–317
Tai IT, Dai M et al (2005) Genome-wide expression analysis of therapy-resistant tumors reveals SPARC as a novel target for cancer therapy. J Clin Invest 115(6):1492–1502
Takeno A, Takemasa I et al (2008) Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis. Br J Cancer 99(8):1307–1315
Tang MJ, Tai IT (2007) A novel interaction between procaspase 8 and SPARC enhances apoptosis and potentiates chemotherapy sensitivity in colorectal cancers. J Biol Chem 282(47):34457–34467
Termine JD, Kleinman HK et al (1981) Osteonectin, a bone-specific protein linking mineral to collagen. Cell 26(1 Pt 1):99–105
Thomas R, True LD et al (2000) Differential expression of osteonectin/SPARC during human prostate cancer progression. Clin Cancer Res 6(3):1140–1149
Tremble PM, Lane TF et al (1993) SPARC, a secreted protein associated with morphogenesis and tissue remodeling, induces expression of metalloproteinases in fibroblasts through a novel extracellular matrix-dependent pathway. J Cell Biol 121(6):1433–1444
Tsuji T, Ibaragi S (2009) Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res 69(18):7135–7139
Vadlamuri SV, Media J et al (2003) SPARC affects glioma cell growth differently when grown on brain ECM proteins in vitro under standard versus reduced-serum stress conditions. Neuro Oncol 5(4):244–254
Vial E, Castellazzi M (2000) Down-regulation of the extracellular matrix protein SPARC in vSrc- and vJun-transformed chick embryo fibroblasts contributes to tumor formation in vivo. Oncogene 19(14):1772–1782
Wang CS, Lin KH et al (2004) Overexpression of SPARC gene in human gastric carcinoma and its clinic-pathologic significance. Br J Cancer 91(11):1924–1930
Watkins G, Douglas-Jones A et al (2005) Increased levels of SPARC (osteonectin) in human breast cancer tissues and its association with clinical outcomes. Prostaglandins Leukot Essent Fatty Acids 72(4):267–272
Wessel C, Westhoff CC et al (2008) CD34(+) fibrocytes in melanocytic nevi and malignant melanomas of the skin. Virchows Arch 453(5):485–489
Wiese AH, Auer J et al (2007) Identification of gene signatures for invasive colorectal tumor cells. Cancer Detect Prev 31(4):282–295
Wong FH, Huang CY et al (2009) Combination of microarray profiling and protein-protein interaction databases delineates the minimal discriminators as a metastasis network for esophageal squamous cell carcinoma. Int J Oncol 34(1):117–128
Xue LY, Hu N et al (2006) Tissue microarray analysis reveals a tight correlation between protein expression pattern and progression of esophageal squamous cell carcinoma. BMC Cancer 6:296
Yamanaka M, Kanda K et al (2001) Analysis of the gene expression of SPARC and its prognostic value for bladder cancer. J Urol 166(6):2495–2499
Yamashita K, Upadhay S et al (2003) Clinical significance of secreted protein acidic and rich in cystein in esophageal carcinoma and its relation to carcinoma progression. Cancer 97(10):2412–2419
Yan Q, Weaver M et al (2005) Matricellular protein SPARC is translocated to the nuclei of immortalized murine lens epithelial cells. J Cell Physiol 203(1):286–294
Yang E, Kang HJ et al (2007) Frequent inactivation of SPARC by promoter hypermethylation in colon cancers. Int J Cancer 121(3):567–575
Yiu GK, Chan WY et al (2001) SPARC (secreted protein acidic and rich in cysteine) induces apoptosis in ovarian cancer cells. Am J Pathol 159(2):609–622
Yunker CK, Golembieski W et al (2008) SPARC-induced increase in glioma matrix and decrease in vascularity are associated with reduced VEGF expression and secretion. Int J Cancer 122(12):2735–2743
Zeltner L, Schittenhelm J et al (2007) The astrocytic response towards invasive meningiomas. Neuropathol Appl Neurobiol 33(2):163–168
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2011 Springer Science+Business Media B.V.
About this chapter
Cite this chapter
Thomas, S.L., Rempel, S.A. (2011). SPARC and the Tumor Microenvironment. In: Mueller, M., Fusenig, N. (eds) Tumor-Associated Fibroblasts and their Matrix. The Tumor Microenvironment, vol 4. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0659-0_17
Download citation
DOI: https://doi.org/10.1007/978-94-007-0659-0_17
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-0658-3
Online ISBN: 978-94-007-0659-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)