Stromal expression of matrix metalloproteinase 2 in cancer-associated fibroblasts is strongly related to human epidermal growth factor receptor 2 status in invasive breast carcinoma

Abstract

Abstract. The peritumoral stroma and cancer-associated fibroblasts (CAFs) have been suggested to play an important role in breast tumorigenesis. The specific immunohistochemical characteristics of the stromal component according to the breast carcinoma subtype surrogates of molecular classes is poorly understood. In the present study, immunohistochemical staining was used to evaluate the expression of matrix metalloproteinase 2 (MMP2), which is one of the most important proteins considered to facilitate tumor invasion, in a series of invasive breast carcinomas according to subtype: Luminal A, luminal B, luminal-HER2, HER2-enriched and triple-negative. A significant increase in MMP2 expression was demonstrated in tumors known to exhibit a more aggressive metastatic behavior, such as luminal HER2 (37%), HER2-enriched (30%) and triple-negative tumors (17%), compared with the luminal A (6%) or luminal B (13%) subtypes. Our data indicated that the CAFs associated with different breast subtypes exhibit different specific properties to facilitate tumor invasion.

Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer

“…CAF-related proteins, such as fibroblast activation protein alpha (FAPα), podoplanin, S100A4, platelet-derived growth factor receptor alpha (PDGFRα), and PDGFRβ, were found to be upregulated in HER2-overexpressing patients (38). The expression of matrix metalloproteinase 2 (MMP2), which facilitates tumor invasion, has been shown to be significantly increased in HER2 subtype patients but not in TNBC patients (39). In ER+ cases, hormone therapy remains the most important therapy; however, acquired resistance to endocrine therapy is a clinical obstacle.…”

Gustoća limfnih i malih krvnih žila u stromi tumora i peritumoralnog tkiva u invazivnom karcinomu dojke bez posebnih obilježja

“…These changes are in accordance with the role of CAFs in tumor spread and their role in tumor stroma infi ltration and metastasis. As far as is known today, this role seems to be one of the most important for tumor agressiveness (41)(42)(43). Therefore, it seems plausible that the growth factors as well as others, still not complely understood soluble mediators produced and excreted by CAFs may have a role in both angio and lymphangiogenesis in breast carcinoma.…”

Preexposure of MCF-7 breast cancer cell line to dexamethasone alters the cytotoxic effect of paclitaxel but not 5-fluorouracil or epirubicin chemotherapy

“…Indeed, it has been proposed that the peritumoral stroma and cancer-associated fibroblasts play an important role in breast tumorigenesis 17,24. For example, in tumors that exhibit an aggressive metastatic phenotype, such as luminal HER2-positive and triple-negative, metallo-proteinase-2 (MMP-2) expression is significantly increased 25. Dex could be acting at this level, by alleviating the effect of MMP-2 19,26.…”

“… 17 , 24 For example, in tumors that exhibit an aggressive metastatic phenotype, such as luminal HER2-positive and triple-negative, metallo-proteinase-2 (MMP-2) expression is significantly increased. 25 Dex could be acting at this level, by alleviating the effect of MMP-2. 19 , 26 More recently, we demonstrated frequent expression of GRs in breast cancer-associated fibroblasts.…”