Fibroblast-breast cancer cells' interaction and Chemerin expression

DORİNA RAMA

Fibroblast-breast cancer cells' interaction and Chemerin expression

Thesis Type: Doctorate

Institution Of The Thesis: Hacettepe Üniversitesi, Sağlık Bilimleri Enstitüsü, Temel Onkoloji A.B.D., Turkey

Approval Date: 2011

Thesis Language: English

Student: DORİNA RAMA

Principal Supervisor (For Co-Supervisor Theses): DİCLE GÜÇ, GÜNEŞ ESENDAĞLI

Open Archive Collection: AVESIS Open Access Collection

Abstract:

Cellular components of the microenvironment interact and influence the tumor growth and differentiation through communication via various molecules like growth factors, cytokines and chemokines. Chemerin is a newly characterized chemotactic peptide acting on chemokine-like receptor 1 (CMKLR1) expressing cells. In addition, chemerin can play both pro- and anti-inflammatory roles directly. In this study the tumor microenvironment was modeled in vitro in 2D and 3D culture systems by using 4T1 tumor, NIH/3T3 and 3T3-L1 fibroblast, and J744A.1 monocyte/macrophage cell lines. Chemerin expression in fibroblasts was modulated by 4T1 and J744A.1 co-cultures. CMKLR1 was expressed by fibroblasts and J744A.1 cells. CMKLR1 expression by J744A.1 was determined to be associated with the fibroblast-assisted maturation of J744A.1 monocyte/macrophage cells in the co-cultures, whereas the presence of tumor cells was able to upregulate CMKLR1 expression independent of macrophage maturation. In addition, macrophages cultured with tumor cells or in tumor cell-conditioned media responded to bioactive chemerin(17-165) peptide and increased the expression of pro-inflammatory cytokines like IL-1ß, TNF- ? and IL-12 p40. Co-cultures of 4T1 with NIH/3T3, or with 3T3-L1 and J744A.1 increased cell proliferation and colony formation. 4T1 cells co-cultured with 3T3-L1 gained a fusiform shape. Administration of bioactive chemerin(17-156) peptide decreased 4T1 proliferation, and number and size of colonies in co-cultures. These observations may indicate a potential role for chemerin and its receptor CMKLR1 in the regulation of tumor microenvironment.