ABSTRACT
Several studies have confirmed that the breast tumor microenvironment drives cancer progression and metastatic development. The aim of our research was to investigate the prognostic significance of the breast tumor microenvironment in untreated early breast cancer patients. Therefore, we analyzed the association of the expression of α-SMA, FSP, CD105 and CD146 in CD34-negative spindle-shaped stromal cells, not associated with the vasculature, in primary breast tumors with classical prognostic marker levels, metastatic recurrence, local relapse, disease-free survival, metastasis-free survival and the overall survival of patients. In the same way, we evaluated the association of the amount of intra-tumor stroma, fibroblasts, collagen deposition, lymphocytic infiltration and myxoid changes in these samples with the clinical-pathological data previously described. This study is the first to demonstrate the high CD105 expression in this stromal cell type as a possible independent marker of unfavorable prognosis in early breast cancer patients. Our study suggests that this new finding can be useful prognostic marker in the clinical-pathological routine.
Subject(s)
Antigens, CD34/metabolism , Antigens, CD/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Receptors, Cell Surface/metabolism , Actins/metabolism , Adult , Aged , Aged, 80 and over , Breast Neoplasms/diagnosis , CD146 Antigen/metabolism , Disease-Free Survival , Endoglin , Female , Humans , Middle Aged , Neoplasm Metastasis , Recurrence , Retrospective Studies , Stromal Cells/metabolism , Stromal Cells/pathology , Tumor MicroenvironmentABSTRACT
Bone metastasis is an incurable complication of breast cancer affecting 70-80 % of advanced patients. It is a multistep process that includes tumour cell mobilisation, intravasation, survival in the circulation, extravasation, migration and proliferation in the bone marrow/bone. Although novel findings demonstrate the bone marrow microenvironment significance in bone metastatic progression, a majority of studies have focused on end-stage disease and little is known about how the pre-metastatic niche arises in the bone marrow/bone tissues. We demonstrated a significant increase in patients' peripheral blood plasma ability to induce transendothelial migration of MCF-7 cells compared with healthy volunteers. Moreover, high RANKL, MIF and OPG levels in patients' peripheral blood could play a role in the intravasation, angiogenesis, survival and epithelial-mesenchymal transition of circulating tumour cells. Also, we observed a significant increase in patients' bone marrow plasma capacity to induce transendothelial migration of MDA-MB231 and MCF-7 cells compared with healthy volunteers. Furthermore, patients' bone marrow mesenchymal stem cells could control the recruitment of tumour cells, modifying the MCF-7 and MDA-MB231 cell migration. In addition, we found a significantly higher MDA-MB231 cell proliferation when we used patients' bone marrow plasma compared with healthy volunteers. Interestingly, PDGF-AB, ICAM-1 and VCAM-1 levels in patients' bone marrow were significantly higher than the values of healthy volunteers, suggesting that they could be involved in the cancer cell extravasation, bone resorption and cancer cell proliferation. We believe that these results can reveal new information about what alterations happen in the bone marrow of advanced breast cancer patients before bone colonisation, changes that create optimal soil for the metastatic cascade progression.
Subject(s)
Bone Marrow/pathology , Bone Neoplasms/secondary , Breast Neoplasms/pathology , Apoptosis , Bone Neoplasms/blood , Breast Neoplasms/blood , Cell Line, Tumor , Cell Proliferation , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunohistochemistry , Neoplasm MetastasisABSTRACT
BACKGROUND/AIMS: Adipose microenvironment is involved in signaling pathways that influence prostate cancer (PCa) progression. However, the role of human periprostatic adipose tissue (PPAT) from patients with benign prostatic hyperplasia (BPH) has not been studied and compared to that of PPAT from PCa patients. The aim of this paper was to investigate the influence of factors derived from both PPATs on the behavior of androgen-dependent and castration resistant PCa cells. METHODS: PPAT conditioned media (CM) were obtained from tissue samples from patients with clinically primary PCa (TPPAT) or BPH (BPPAT). Cell adhesion, proliferation, migration and metalloproteinase expression were evaluated following exposure of LNCaP (androgen dependent) and PC3 (androgen independent) prostate cancer cell lines to BPPAT or TPPAT CM. RESULTS: Proliferation or motility of LNCaP or PC3 cells were not significantly affected by TPPAT or BPPAT CM. The number of LNCaP but not PC3 cells attached to components of TPPAT CM significantly decreased compared to cells attached to BPPAT CM. PPAT produced and released pro-MMP-9. Zymograms demonstrated that TPPAT CM induced a significant increase in pro-MMP-9 activity compared to BPPAT CM in LNCaP cells but not in PC3 cells. CONCLUSIONS: We conclude that TPPAT released factors, such as pro-MMP-9, could induce the invasive capacity of LNCaP cells and speculate that PPAT derived factors could, in the early stages of prostate cancer, modulate disease progression.
