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

Abstract

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.

Prognostic impact of tumour‐infiltrating B cells and plasma cells in colorectal cancer

“…Conversely, tumour cell‐specific CD138 expression was an independent predictor of poor patient outcome. This is in line with the previously reported association between high stromal‐ or tumour‐specific CD138 expression and an impaired prognosis in several cancer types, including CRC . Tumour‐specific and/or stromal CD138 expression has been shown to affect several steps of cell proliferation, transformation and metastasis in CRC .…”

“…This is in line with the previously reported association between high stromal-or tumourspecific CD138 expression and an impaired prognosis in several cancer types, including CRC. 20 Tumour-specific and/or stromal CD138 expression has been shown to affect several steps of cell proliferation, transformation and metastasis in CRC. 46,47 Thus, the biological functions of CD138 appear to depend on the cellular context.…”

“…Conversely, high immune cell-specific CD138 expression has been identified as an independent prognostic marker for shorter survival in breast cancer, 19 and tumour-specific CD138 expression has been found to correlate with poor patient outcome in a few cancer forms, including CRC. 20 To the best of our knowledge, immune cellspecific CD138 expression has hitherto not been investigated in CRC.…”

Syndecan-1 Overexpression Is Associated With Nonluminal Subtypes and Poor Prognosis in Advanced Breast Cancer

“…Syndecan-1 is associated with angiogenic phenotype in colorectal carcinoma, multiple myeloma, and endometrial cancer. [38][39][40][41] Interruption of the interaction of syndecan-1 with integrin αvβ3 and αvβ5, transmembrane receptors critical in angiogenesis, blocks angiogenesis in human vascular endothelial cells in vitro and mouse mammary tumors in vivo and impairs mammary tumor growth in an orthotopic mouse tumor model. 42 Other potential mechanisms include epithelial to mesenchymal transition (EMT), a complex transdifferentiation process that can be divided into 3 types based on context: (1) epithelial-mesenchymal transition (type 1), (2) epithelial-fibroblast transition (type 2), and (3) carcinoma-metastatic transition (type 3).…”

The Role of Syndecan-1 in Cellular Signaling and its Effects on Heparan Sulfate Biosynthesis in Mesenchymal Tumors

“…Hovewer, low cell surface syndecan-1 level is associated with a poor prognosis as demonstrated by immunohistochemistry in lung cancer (51), renal carcinomas (52), head and neck cancer (53), and in colorectal cancer (54, 55). In squamous cell carcinoma of the tonsil the level of syndecan-1 was found lower than in the benign keratoacanthoma and it correlated inversely with the proliferative index (56).…”