Oncotarget

Research Papers:

RANTES and IL-6 cooperate in inducing a more aggressive phenotype in breast cancer cells

Marianna Gallo, Daniela Frezzetti, Cristin Roma, Nicoletta Chicchinelli, Antonio Barbieri, Claudio Arra, Giosuè Scognamiglio, Gerardo Botti, Antonella De Luca _ and Nicola Normanno

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Oncotarget. 2018; 9:17543-17553. https://doi.org/10.18632/oncotarget.24784

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Abstract

Marianna Gallo1, Daniela Frezzetti1, Cristin Roma1, Nicoletta Chicchinelli1, Antonio Barbieri2, Claudio Arra2, Giosuè Scognamiglio3, Gerardo Botti3, Antonella De Luca1 and Nicola Normanno1

1Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, Italy

2Animal Facility, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, Italy

3Surgical Pathology Unit, Istituto Nazionale Tumori-IRCCS-“Fondazione G. Pascale”, Naples, Italy

Correspondence to:

Antonella De Luca, email: [email protected]; [email protected]

Keywords: breast cancer; RANTES/CCL5; IL6; metastasis; tumor microenvironment

Received: July 20, 2017     Accepted: February 26, 2018     Published: April 03, 2018

ABSTRACT

Both the CC chemokine ligand 5 (CCL5/RANTES) and interleukin-6 (IL-6), released by mesenchymal stem cells (MSCs) as well as by neoplastic cells, promote breast cancer cell progression through autocrine and paracrine mechanisms. In order to assess the effects of the simultaneous overexpression of RANTES and IL-6 on the tumor cell phenotype, we overexpressed both proteins in MCF-7 and MDA-MB-231 human breast cancer cell lines. MCF-7 cells co-expressing RANTES and IL-6 had a greater ability to form colonies in soft agar, compared to cells overexpressing RANTES or IL-6. In addition, both MCF-7 and MDA-MB-231 clones co-expressing RANTES and IL-6 showed a significantly higher ability to migrate and to invade. The analysis of phosphorylated ERK1/2, AKT and STAT3 signal transduction proteins revealed that several signaling pathways are simultaneously activated in cells overexpressing both factors. Finally, the overexpression of RANTES and IL-6 in MCF-7 cells significantly increased the in vivo tumor growth. Collectively, our data suggest that the simultaneous expression of IL-6 and RANTES produces a more aggressive phenotype in breast cancer cells and provide evidence that IL-6 and RANTES might represent potential targets for novel therapeutic strategies aimed to block the tumor-stroma interaction.


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