Abstract
BackgroundMatrix metalloproteinases (MMPs) are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. The aim of this study was to assess correlation between CTCs and tumor MMP1 in BC.MethodsStudy included 149 primary BC patients treated by surgery from March 2012 to March 2013. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSepTM selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, ZEB1) and epithelial (CK19) gene transcripts by qRT-PCR. Patient samples with higher epithelial and/or mesenchymal gene transcripts than those of healthy donors (n = 60) were considered as CTC positive. Expression of MMP1 in surgical specimens was evaluated by immunohistochemistry.ResultsCTCs were detected in 24.2% patients. CTCs exhibiting only epithelial markers were present in 8.7% patients, whereas CTCs with epithelial-mesenchymal transition (EMT) markers (CTC_EMT) were observed in 13.4% of patients and CTCs co-expressing both markers were detected in 2.0% patients. Patients with CTC_EMT in peripheral blood had significantly increased expression of MMP1 in tumor cells (p = 0.02) and tumor associated stroma (p = 0.05) than those of patients without CTC_EMT. In multivariate analysis, CTC_EMT and tumor grade were independently associated with MMP1 expression in cancer cells, while CTC_EMT and Ki67 were independently associated with MMP1 expression in cancer associated stroma.ConclusionOur data suggest link between MMP1 and CTCs with EMT phenotype and support role of MMPs and EMT in tumor dissemination.
Highlights
Matrix metalloproteinases (MMPs) are involved in cancer invasion and metastasis
The study population consisted of 149 primary breast cancer patients with median age of 60 years
Relative to the highest levels of Snail and Zeb1 transcripts detected in Healthy donors (HD) samples, none of the patient samples overexpressed these gene transcripts
Summary
Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Circulating tumor cells (CTCs) play an important role in the metastatic cascade, cancer dissemination and progression. MMP1 cleave extracellular matrix components and play an important role in tumor invasion [8]. Many studies suggest that overexpression of MMPs is one of the key events leading to the breast cancer dissemination. It was shown, that MMPs induce epithelial to mesenchymal transition and increase the invasive potential of tumor cells [11,12]
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