Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components

Ioachim, Elli; Michael, MC; Salmas, Marios; Damala, K; Tsanou, Elena; Michael, MM; Malamou-Mitsi, Vasiliki; Stavropoulos, Nikolaos

doi:10.1186/1471-2407-6-140

Cited by 71 publications

(64 citation statements)

References 48 publications

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“…Some researches in their studies found that TSP-1 was distributed in the cytoplasm of tumor cells in thyroid cancer [31], breast cancer [32], hepatocellular carcinoma [33], gastric carcinoma [34], and CRC [19]; while others studies showed that TSP-1 was mainly expressed in the ECM in pancreatic cancer [35], CRC [16], esophageal squamous cell carcinoma [36], non-small cell lung cancer [10], ductal in situ carcinoma of the breast [37]. However, others studies reported TSP-1 expression in both cytoplasm and stroma, as well in CRC [9], bladder cancer [13], and breast cancer [38]. Thus, the expression mode of TSP-1 in tumors could vary in different tissues or organs.…”

Section: Discussionmentioning

confidence: 99%

“…There is a close relationship between the expression of TSP-1 and wild-type p53, in the manner that loss of wild-type p53 being associated with loss of TSP-1 expression [8,9]. Decreased expression of the TSP-1 is correlated with metastatic potential in prostate cancer [10], non-small lung cancer [11], breast cancer [12], and bladder cancer [13]. In CRC, TSP-1 has been shown to have both an angiogenic effect [14,15] and conversely be associated with venous invasion and tumour progression [16].…”

Section: Introductionmentioning

confidence: 99%

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Association Between Thrombospondin-1, Angiogenesis Related Markers, and Extracellular Matrix Components with Colorectal Cancer Outcome

Mitselou¹,

Arvanitis²,

Skoufi³

et al. 2013

TOCOLCJ

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Abstract:Background: Angiogenesis is a multistep process that depends on the balance of proangiogenic factors and inhibitors as well as on interactions with the extracellular matrix. Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis encoded by THBS1 gene, whose promoter is activated by p53. Aim:To evaluate the relevance of TSP-1 in patients with colorectal cancer. Material and Methods:We examined the immunohistochemical expression of angiogenic agents (VEGF and CD34), proliferation associated indices, extracellular matrix components (tenascin, fibronectin, laminin, and collagen type IV), and the antiangiogenic agent TPS-1 in 97 patients with colorectal carcinoma (CRC) and correlated their expression levels with clinicopathological parameters.Results: TSP-1 was detected in the tumor cells, stroma and perivascular tissue. High and moderate tumor TSP-1 expression was observed in 24.75%, weak in 19.6%, while 55.7% of the cases were negative. High stromal expression was observed in 40.2% and perivascular stain was noted in 31.95% of the cases. Stromal TSP-1 expression was correlated with tumor type and tumor grade (p=0.001, and p=0.041 respectively) and with ECM components expression: tenascin (p=0.053), fibronectin (p=0.063), collagen type IV (p=0.004) and laminin (p=0.0001). The relationship of TSP-1 expression with tumor angiogenesis, growth fraction, p53 protein expression, and overall survival was not significant. Conclusions:Our data suggest that both tumor and stromal TSP-1 expression may not be a direct antiangiogenic factor, although it seems to be implicated in the remodeling of colorectal cancer tissue through interaction with other extracellular matrix components.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association Between Thrombospondin-1, Angiogenesis Related Markers, and Extracellular Matrix Components with Colorectal Cancer Outcome

Mitselou¹,

Arvanitis²,

Skoufi³

et al. 2013

TOCOLCJ

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“…However, other investigators showed the expression of DPD, TP or OPRT to be correlated with various clinicopathological factors, prognosis and efficacy of 5-FU agents (14,(25)(26)(27)(28). Although the reason for these discrepancies was unclear, trials to verify prognosis and efficacy of the 5-FU agents while taking clinicopathological factors into account are a crucial strategic objective to further validate useful biomarkers.…”

Section: Discussionmentioning

confidence: 99%

A retrospective study on TS mRNA expression and prediction of the effects of adjuvant oral 5-fluorouracil in breast cancer

Aki¹,

Bando²,

Takahashi³

et al. 2010

Oncology Letters

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Abstract. Nucleic acid-metabolizing enzymes, such as thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP) and orotate phosphoribosyl transferase (OPRT), have attracted attention as candidates for response determinants of 5-fluorouracil (5-FU). Whether the expression levels of these enzymes can be adopted as valuable parameters for 5-FU sensitivity in breast cancer has yet to be elucidated. In the present study, intratumoral mRNA expression of TS, DPD, TP and OPRT were determined in formalin-fixed paraffin-embedded surgical specimens collected from 217 breast cancer patients, using the Danenberg Tumor Profile method, which combines microdissection and real-time-polymerase chain reaction. The significance of these enzymes as prognostic and 5-FU efficacy-predicting factors was evaluated. Our data showed that a low DPD expression is related to a high nuclear grade and other factors including hormone receptor-negativity. Low expression levels of TP were found in hormone receptornegative tumors. TS and OPRT expression were not related to various clinicopathological factors, but patients with a high TS mRNA expression showed a significantly poorer prognosis in cases where 5-FU was not administered. The efficacy of 5-FU was more significant when administered for more than 6 months in the group with a high TS mRNA expression. These data suggest that TS mRNA expression in breast cancer tissue is an ideal predictor of outcomes for patients with no administration of 5-FU, and of the efficacy of 5-FU.

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“…[22,23,27] Thrombospondin-1 is expressed in the stroma and cancer cells. [70] TNC, a key metastatic niche molecule required for the metastasis initiation, is also expressed in breast tumor cells and stroma cells. [8,16,18] Collagens are mainly synthesized by cancer-associated fibroblasts in breast cancer, but cancer cells are also an important source of the collagen.…”

Section: Cancer Cells Are Critical Sources Of Tumor Ecmmentioning

confidence: 99%

Function of cancer cell-derived extracellular matrix in tumor progression

Xiong¹,

Xu²

2016

JCMT

113

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How to cite this article: Xiong GF, Xu R. Function of cancer cell-derived extracellular matrix in tumor progression. J Cancer Metasta Treat 2016;2:357-64.Extracellular matrix (ECM) is an essential component of the tumor microenvironment. Cancer development and progression are associated with increased ECM deposition and crosslink. The chemical and physical signals elicited from ECM are necessary for cancer cell proliferation and invasion. It is well recognized that stromal cells are a major source of ECM proteins. However, recent studies showed that cancer cells are also an active and important component in ECM remodeling. Cancer cells deposit a significant amount of collagen, fibronectin, and tenascin C (TNC). Recent studies demonstrate that these cancer cell-derived ECM proteins enhance cancer cell survival and promote cancer cell colonization at distant sites. ECM-related enzymes and chaperone proteins, such as prolyl-4-hydroxylase, lysyl-hydroxylase, lysyl oxidase, and heat shock protein 47, are also highly expressed in cancer cells. Inhibition of these enzymes significantly reduces cancer growth, invasion, and metastasis. These factors suggest that the cancer cell-derived ECM is crucial for cancer progression and metastasis. Therefore, targeting these ECM proteins and ECM-related enzymes is a potential strategy for cancer treatment. Key words:Tumor microenvironment, extracellular matrix, cancer progression, metastasis ABSTRACT Article history:

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Thrombospondin-1 expression in urothelial carcinoma: prognostic significance and association with p53 alterations, tumour angiogenesis and extracellular matrix components

Cited by 71 publications

References 48 publications

Association Between Thrombospondin-1, Angiogenesis Related Markers, and Extracellular Matrix Components with Colorectal Cancer Outcome

Association Between Thrombospondin-1, Angiogenesis Related Markers, and Extracellular Matrix Components with Colorectal Cancer Outcome

A retrospective study on TS mRNA expression and prediction of the effects of adjuvant oral 5-fluorouracil in breast cancer

Function of cancer cell-derived extracellular matrix in tumor progression

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