Abstract

The communication between the tumor cells and the surrounding cells helps drive the process of tumor progression. Since the microenvironment of breast cancer includes CCL20 chemokine, the purpose of this study was to determine whether CCL20 modulates the physiology of healthy breast epithelial cells in areas adjacent to the tumor. Therefore, primary cultures of mammary cells taken from normal peritumoral areaswere used.We assessed that breast cells expressedCCR6CCL20 receptor.Usingmolecular (siRNA) and pharmacological (inhibitors) techniques, we found multiple signaling kinases to be activated by CCR6 and involved in CCL20-induced breast cell proliferation and migration. The binding of 10 ng/ml CCL20 to CCR6 induced cell migration whilst higher concentrations (from 15 to 25 ng/ml) led to cell proliferation. CCL20 controlled cell migration and MMP-9 expression by PKC-alpha that activated Src, which caused the activation of downstream Akt, JNK, and NF-kB pathways. Furthermore, higher CCL20 concentrations increased cycE and decreased p27Kip expression ending in enhanced cell proliferation.Cell proliferation occurred through PKC-epsilon activation that transactivated EGFR and ERK1/2/MAPK pathway.Although activated by differentCCL20 concentrations, these pathways function in parallel and crosstalk to some extent, inasmuch as Akt activation was responsible for ERK1/2 nuclear translocation and enhanced the transcription of of c-fos and c-myc, involved in cell proliferation. In summary, tumor cells exchange signals with the surrounding healthy cellsmodifying the extracellular matrix through enzyme secretion; thus, CCL20 might be a factor involved in the ontogeny of breast carcinoma.

Autore Pugliese

• Muscella Antonella , Marsigliante Santo

Tutti gli autori

• S. Marsigliante , C. Vetrugno , A. Muscella

Titolo volume/Rivista

JOURNAL OF CELLULAR PHYSIOLOGY

Anno di pubblicazione

2013

ISSN

0021-9541

ISBN

Non Disponibile

Numero di citazioni Wos

35

Ultimo Aggiornamento Citazioni

28/04/2018

Numero di citazioni Scopus

37

Ultimo Aggiornamento Citazioni

28/04/2018

Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile