Podoplanin expression in cancer-associated fibroblasts correlates with VEGF-C expression in cancer cells of invasive ductal breast carcinoma

Abstract

Podoplanin (D2-40) was shown to be expressed in cancer-associated fibroblasts (CAFs) of various malignancies. The study aimed at examining its impact on angiogenesis and lymphangiogenesis markers in invasive ductal carcinoma of the breast (IDC). The studies were performed on 104 archival cases of IDC using immunohistochemical technique. Podoplanin expression in CAFs correlated positively with cancer cell VEGF-C expression (r=0.19, p=0.0495) and intratumoral microvessel count (MVC) of CD31 positive vessels (r=0.30, p=0.0018), whereas negative correlations were observed with peritumoral MVC of D2-40 and Lyve-1 positive lymphatic vessels (r=-0.26, p=0.008 and r=-0.27, p=0.0058, respectively). Podoplanin expression in CAFs did not correlate with VEGF-A and VEGF-D expression in cancer cells, nor exerted any prognostic significance. Podoplanin expression in CAFs may have impact on angio-and lymphangiogenesis processes in IDC.

Cancer-associated fibroblasts: A multifaceted driver of breast cancer progression

“…In this regard, mCAFs are also probably co-contributors to lymphangiogenesis, since the presence of mCAFs was associated with lymphatic density in addition to lymphatic invasion and nodal status [30,42,44,46]. Interestingly, podoplanin expression in mCAFs significantly correlates with VEGF-C expression in cancer cells of invasive ductal breast carcinoma [134]. Moreover, mCAFs were observed to promote intratumoral lymphangiogenesis via a hyaluronan-dependent manner in nude mice [135].…”

Cancer-Associated Fibroblasts as Another Polarized Cell Type of the Tumor Microenvironment

“…A recent study by Orr et al, revealed additional markers such as ASPN, ZEB1, and OGN that distinguish prostate CAFs from their normal counterparts (15). The glycoprotein podoplanin was also suggested as another, novel CAF-marker that has been shown to have prognostic significance for different types of tumors (16, 17). However, all the CAF markers described so far are apparently not unique for this cell type and are expressed by other cell types of a tumor, reflecting the plasticity of stromal cells.…”

Molecular Mechanisms Underlying Lymphovascular Invasion in Invasive Breast Cancer

“…Some studies have reported an association between podoplanin expression by CAFs in BC and aggressive features including LVI, node metastasis and poor outcome [55]. Podoplanin expression in CAFs is also correlated with BC cell VEGFC expression and intratumoural microvessel count [56]. Interestingly, high podoplanin expression at the invasive front of BC plays an alternative role in invasion and metastasis by forming invasive protrusions and filopodia without activation of endothelial-mesenchymal transition [55].…”