Thrombospondin-1 Expression in Bladder Cancer: Association With p53 Alterations, Tumor Angiogenesis, and Tumor Progression

Grossfeld, Gary D.; Ginsberg, David A.; Stein, John P.; Bochner, Bernard H.; Esrig, David; Groshen, Susan; Dunn, Meleana; Nichols, Peter W.; Taylor, Clive R.; Skinner, Donald G.; Côté, Richard J.

doi:10.1093/jnci/89.3.219

Cited by 289 publications

(194 citation statements)

References 29 publications

Supporting

Mentioning

168

Contrasting

Unclassified

Order By: Relevance

“…For example, the expression of cadherins (Takeichi, 1993), SPARC (Jendraschak and Sage, 1996), laminin (Mizushima et al, 1996), thrombospondin (Grossfeld et al, 1997), protein tyrosine phosphatase (CL100) (Loda et al, 1996), and MAGE proteins (Itoh et al, 1996), have been reported to be altered in tumors. It is not known whether any genes identi®ed in this study can be causally linked to the carcinogenesis, but several genes, such as AA112374 (see Figure 6d) that are preferentially expressed in cancer cell lines represent potential candidates.…”

Section: Discussionmentioning

confidence: 99%

Characterization of transformation related genes in oral cancer cells

Chang

Park²,

Denny

et al. 1998

Oncogene

View full text Add to dashboard Cite

A cDNA representational di erence analysis (cDNA-RDA) and an arrayed ®lter technique were used to characterize transformation-related genes in oral cancer. From an initial comparison of normal oral epithelial cells and a human papilloma virus (HPV)-immortalized oral epithelial cell line, we obtained 384 di erentially expressed gene fragments and arrayed them on a ®lter. Two hundred and twelve redundant clones were identi®ed by three rounds of back hybridization. Sequence analysis of the remaining clones revealed 99 unique clones corresponding to 69 genes. The expression of these transformation related gene fragments in three nontumorigenic HPV-immortalized oral epithelial cell lines and three oral cancer cell lines were simultaneously monitored using a cDNA array hybridization. Although there was a considerable cell line-to-cell line variability in the expression of these clones, a reliable prediction of their expression could be made from the cDNA array hybridization. Our study demonstrates the utility of combining cDNA-RDA and arrayed ®lters in highthroughput gene expression di erence analysis. The di erentially expressed genes identi®ed in this study should be informative in studying oral epithelial cell carcinogenesis.

show abstract

Section: Discussionmentioning

confidence: 99%

Characterization of transformation related genes in oral cancer cells

Chang

Park²,

Denny

et al. 1998

Oncogene

View full text Add to dashboard Cite

show abstract

“…Several studies have implicated alterations in THBS1 expression in the neovascularization observed in human cancers (Roberts, 1996): Decreased expression of THBS1 has been reported in multiple primary tumors (Grossfeld et al, 1997;Zabrenetzky et al, 1994;Clezardin et al, 1993) and cells transformed in vitro by c-jun (Mettouchi et al, 1994), Nickel (Salnikow et al, 1994), v-src (Slack and Bornstein, 1994), the polyoma virus middle-t antigen (Sheibani and Frazier, 1995), and v-myc (Tikhonenko et al, 1996). Reexpression of THBS1 reduced tumor growth, angiogenesis and metastasis in a hemangioma cell line (Sheibani and Frazier, 1995) and a breast cancer cell line (WeinstatSaslow et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Methylation and silencing of the Thrombospondin-1 promoter in human cancer

et al. 1999

View full text Add to dashboard Cite

Neovascularization is a common feature of many human cancers, but relatively few molecular defects have been demonstrated in genes regulating angiogenesis. Decreased expression of Thrombospondin-1 (THBS1), a P53 and Rb regulated angiogenesis inhibitor, has been observed in some human tumors, including glioblastoma multiforme (GBM). To study whether methylationassociated inactivation is involved in down-regulating THBS1 expression in cancer, we analysed the methylation status of THBS1 in several cell lines and primary tumors. Three cell lines (RKO, CEM and RAJI) were completely methylated at several CpG sites within the THBS1 5' CpG island, and had no detectable expression by RT ± PCR. THBS1 expression was readily reactivated using the methylation-inhibitor 5-deoxy-azacytidine in all three lines. Furthermore, THBS1 methylation was present in 33% (14/42) of primary GBMs. Thus, de novo methylation may serve as a potential way to inactivate THBS1 expression in human neoplasms.

show abstract

“…32 TSP1 is expressed in normal breast, colon, and bladder epithelium. 10,[33][34][35] In general, TSP1 expression is significantly reduced in cancer cells that arise in these tissues. However, lobular carcinomas in the breast express significantly higher levels of TSP1 and TSP2 than normal tissue.…”

mentioning

confidence: 99%

“…10,[33][34][35] TSP1 expression shows an inverse correlation with vascular density in bladder and colon cancer but does not correlate with vascular density in some other tissues such as ductal breast carcinoma. 10,[33][34][35] Whereas TSP1 may be down-regulated in tumor cells, relatively high levels of TSP1 and TSP2 mRNA and protein are associated with stromal fibroblasts. 33,36 In addition, activated monocytes and macrophages contribute TSP1 to the tumor environment as do endothelial cells.…”

mentioning

confidence: 99%

Thrombospondin-1 Gene Expression Affects Survival and Tumor Spectrum of p53-Deficient Mice

Lawler

Miao

Duquette

et al. 2001

The American Journal of Pathology

109

View full text Add to dashboard Cite

In vitro and in vivo data indicate that thrombospondin-1 (TSP1) inhibits tumor progression in several ways including direct effects on cellular growth and apoptosis in the stromal compartment. To evaluate the importance of TSP1 for the progression of naturally arising tumors in vivo, we have crossed TSP1-deficient mice with p53-deficient mice. In p53-null mice, the absence of TSP1 decreases survival from 160 ؎ 52 days to 149 ؎ 42 days. A log-rank test comparing survival curves for these two populations yields a two-sided P value of 0.0272. For mice that are heterozygous for the p53-null allele, survival is 500 ؎ 103 days in the presence of TSP1 expression, and 426 ؎ 125 days in its absence (P ‫؍‬ 0.0058). Whereas TSP1 expression did not cause a measurable change in the incidence of the majority of tumor types, a statistically significant (P < 0.05) decrease in the incidence of osteosarcomas is observed in the absence of TSP1. To determine more directly if host TSP1 inhibits tumor growth, B16F10 melanoma and The p53 tumor suppressor gene product is a transcription factor that induces growth arrest and apoptosis. 1 Mutations in the p53 gene are common in human cancers. In the mouse, the complete absence of p53 expression results in a dramatic decrease in survival, with all of the mice succumbing to various types of cancer within 9 months. [2][3][4] Lymphomas are observed with the highest frequency in these mice; however, tumors from a wide range of cell lineages are observed. Mice that are heterozygous for p53 have an increased life span but eventually succumb to a more evenly distributed range of lymphomas, sarcomas, and carcinomas. Thus, mice that are deficient in p53 gene expression are a valuable model for assaying the effects of other gene mutations on the progression of naturally occurring tumors.The loss of p53 function in fibroblasts from patients with Li-Fraumeni Syndrome has been shown to correlate with a reduction in thrombospondin-1 (TSP1) protein expression and a switch in the angiogenic phenotype from inhibitory to stimulatory. 5,6 Moreover, p53 can also regulate TSP1 and angiogenesis in cultured fibroblasts and in some human breast tumors. 7 However, in other tissues, such as brain, skin, and bladder, p53 does not seem to regulate TSP1 expression. 8 -10 The thrombospondins are a family of extracellular calcium-binding proteins. [11][12][13] Of the five family members, TSP1 is the most extensively characterized because it is readily purified from blood platelets. Through its interaction with proteoglycans, other matrix proteins, growth factors, and membrane receptors, TSP1 directs the assembly of multiprotein complexes that modulate cellular phenotype. TSP1 also directly activates transforming growth factor-␤ (TGF-␤) and can affect the activity of various extracellular proteases including plasmin, elastase, and cathepsin. 14 -18 Biological processes frequently involve a balance of stimulatory and inhibitory factors. 19 -21 The multiprotein complexes that are formed on the cell membrane in response...

show abstract

Thrombospondin-1 Expression in Bladder Cancer: Association With p53 Alterations, Tumor Angiogenesis, and Tumor Progression

Cited by 289 publications

References 29 publications

Characterization of transformation related genes in oral cancer cells

Characterization of transformation related genes in oral cancer cells

Methylation and silencing of the Thrombospondin-1 promoter in human cancer

Thrombospondin-1 Gene Expression Affects Survival and Tumor Spectrum of p53-Deficient Mice

Contact Info

Product

Resources

About