559P - Differential association of TGF-β expression with MCP-1 and RANTES expression in primary tumor depending on stages of breast cancer patients from E...

Date 17 December 2016
Event ESMO Asia 2016 Congress
Session Poster lunch
Topics Translational Research
Presenter GUNJAN Mandal
Citation Annals of Oncology (2016) 27 (suppl_9): ix181-ix183. 10.1093/annonc/mdw602
Authors G. Mandal1, S. Biswas1, A. Gupta2, A. Bhattacharyya1
  • 1Zoology, University of Calcutta, 700019 - Kolkata/IN
  • 2Surgical Oncology, Saroj Gupta Cancer Centre & Research Institute, 700063 - Kolkata/IN

Abstract

Background

Transforming Growth Factor beta (TGF-β), a dual role player in progression of breast cancer (BC), acts as both tumor suppressor in early stage and tumor promoter in late stages of the disease. The underlying complex phenomenon is still not clearly explained. The associated tumor and stromal cells produce various growth factors, cytokines and chemokines which support BC progression. The chemoattractant molecules, produced by the tumor cells, bring about the recruitment of those immune cells with specific receptors into the tumor microenvironment. In recent advances, an associated phenomenon with tumor progression is chronic inflammation, where CCL2 (MCP-1) and CCL5 (RANTES) are two key chemokines dwelling with the disease condition. Under the prevailing situation, we aim to explore how the expression of these two chemokines is directed by TGF-β signaling in different stages of BC.

Methods

PCR, Immunohistochemistry, Western Blotting, Immunofluorescence, Flow cytometry, Statistical Analyses.

Results

We observed TGF-β expression is inversely proportional with both CCL2 and CCL5 expression in the early stages of breast cancer but in late stage it is directly proportional with CCL2 expression but not significantly associated with CCL5 expression. CCL2 and CCL5 expression by primary tumor is significantly associated with macrophage and total Th cell percentage, respectively, in the primary tumor tissue. Interestingly, low CCL5 and high CCL2 is correlated with higher percentage of Th2 over Th1 cells within the primary tumor tissue and we observed higher CCL2 induces macrophages to secrete Th2 attracting chemokines CCL17 and CCL22.

Conclusions

Our study describes how TGF-β regulates Th2:Th1 ratio through regulating CCL2, CCL5 expression differently at early and late stages of breast cancer. Higher Th2:Th1 ratio is known for protumor anti-inflammatory response and therefore, TGF-β favors tumor progression during late stages of BC.

Clinical trial indentification

Legal entity responsible for the study

Department of Science and Technology, Government of India

Funding

Department of Science and Technology, Government of India

Disclosure

All authors have declared no conflicts of interest.