Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

Abstract

Cervical carcinoma is the second most frequent cancer type in women worldwide. Both inflammatory cells and stromal cells are important for tumor progression. Stromal cells produce growth factors and extracellular matrix and provide an adequate environment for angiogenesis. Versican, a member of the extracellular matrix, has been shown to have a role in tumor progression. The aim of this study was to investigate versican expression, and its association with tumor-infiltrating inflammatory cell subsets and with clinicopathological parameters in human cervical cancers. We have studied the expression of versican in 149 cervical cancers using immunohistochemistry and mRNA in situ hybridization. Versican was predominantly expressed in the stroma (myofibroblasts). Using quantitative real-time-PCR, V0 was found to be the most prominent isoform. High stromal versican expression was significantly associated with a low number of tumor-infiltrating T cells (P ¼ 0.018) and particularly a low number of CD8-positive T cells (cytotoxic T cells; P ¼ 0.002). Stromal versican expression was significantly higher in patients with an infiltration depth 414 mm (P ¼ 0.004) and in patients with parametrial invasion (P ¼ 0.044). Stromal versican expression was not associated with survival. Our results suggest that versican expression in the stromal compartment of cervical cancers results in reduced numbers of intraepithelial CD8-positive T cells and enhanced local invasion.

ADAMTS5 Is a Critical Regulator of Virus-Specific T Cell Immunity

“…Furthermore, corroborating evidence by others in the field demonstrates that an epitope in the N-terminal globular domain of versican promoted CD4 + T cell migration and lymphocyte rolling [22]. Additionally, versican overexpression was associated with decreased infiltration of CD8 + T cells in stromal compartments of cervical cancer [28]. …”

“…We therefore reasoned that the lack of ADAMTS5 enzymatic activity in the MLN of Adamts5 -/- mice would result in an accumulation of the versican substrate. It is also important to note here that the presence of versican has previously been associated with inhibition of lymphocyte migration [22,28] and may result in T cell accumulation in the MLN (Fig 5A). Moreover, versican upregulation has also been associated with inflammatory stimuli [4,29].…”

Unusual roles of caspase-8 in triple-negative breast cancer cell line MDA-MB-231

“…So, understanding the molecular mechanisms of metastasis initiation and progression may be critical for individualizing new therapeutic strategies. Our results showed that the delayed G0/G1-S-phase transition observed in casp-8-knockdown MDA-MB-231 cells, was accompanied by a powerful increase in the expression of a number of factors (VEGFA, C-MYC, CTNNB1, KLF4, HMGA2, CXCR4, VERSICAN V1 and MMP2) known to strongly promote cell migration and metastasis in numerous tumors (22,23,26,28). This could provide MDA-MB-231 cells with particularly high migratory/metastatic capacity, as suggested by wound healing and Transwell assays, showing that, in comparison with control cells, casp-8 knockdown cells were distinctively more migratory, and by the marked increase in the levels of versican V1, which is known to strongly promote cell migration and invasion in a number of cancer cells.…”

“…Recently, it has been shown that versican, a large chondroitin sulfate proteoglycan belonging to the family of lecticans, strongly promotes cell migration and invasion in a number of cancer cells (22,23). Thus, it was pertinent to verify whether such involvement was also possible in MDA-MB-231 cells.…”

Versican regulates metastasis of epithelial ovarian carcinoma cells and spheroids

“…Primers for detection of V0, V1, V2, and V3 isoforms of VCAN and a housekeeping gene control eukaryotic translation elongation factor 1 alpha 1 (EEF1A1) have been synthesized using previously reported sequences [38]. The primers for mRNA detection of V4 isoform of VCAN were constructed according to requirements for oligonucleotide primers for quantitative real-time PCR using the Primer3 software.…”