Macrophages promote matrix protrusive and invasive function of breast cancer cells via MIP-1β dependent upregulation ofMYO3Agene in breast cancer cells

Abstract

The potential of a tumor cell to metastasize profoundly depends on its microenvironment, or "niche" interactions with local components. Tumor-associated-macrophages (TAMs) are the most abundant subpopulation of tumor stroma and represent a key component of tumor microenvironment. The dynamic interaction of cancer cells with neighboring TAMs actively drive cancer progression and metastatic transformation through intercellular signaling networks that need better elucidation. Thus, current study was planned for discerning paracrine communication networks operational between TAMs, and breast cancer cells with special reference to cancer cell invasion and dissemination to distant sites. Here, we report role of MIP-1β in enhancing invasive potential of metastatic breast cancer MDA-MB-231 and MDA-MB-468 cells. In addition, the poorly metastatic MCF-7 cells were also rendered invasive by MIP-1β. The MIP-1β-driven cancer cell invasion was dependent on upregulated expression levels of MYO3A gene, which encodes an unconventional myosin super-family protein harboring a kinase domain. Ex ovo study employing Chick-embryo-model and in vivo Syngenic 4T1/BALB/c mice-model further corroborated aforementioned in vitro findings, thereby substantiating their physiological relevance. Concordantly, human breast cancer specimen exhibited significant association between mRNA expression levels of MIP-1β and MYO3A. Both, MIP-1β and MYO3A exhibited positive correlation with MMP9, an established molecular determinant of cancer cell invasion. Higher expression of these genes correlated with poor survival of breast cancer patients. Collectively, these results point toward so far undisclosed MIP-1β/MYO3A axis being operational during metastasis, wherein macrophage-derived MIP-1β potentiated cancer cell invasion and metastasis via up regulation of MYO3A gene within cancer cells. Our study exposes opportunities for devising potential anti-metastatic strategies for efficient clinical management of breast cancer.

CC Chemokines in a Tumor: A Review of Pro-Cancer and Anti-Cancer Properties of Receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 Ligands

“…Their expression has been found in tumor-associated and cancer cells. In a tumor, they are produced by TAM [ 69 , 124 , 125 , 126 , 127 ], MDSC [ 68 ], and MSC [ 66 ], which promotes tumor growth. The expression of CCL4 may also occur in tumor-associated neutrophils (TAN) [ 128 ].…”

“…CCL3 causes migration and invasion of cancer cells via CCR5 [ 124 , 127 , 144 ]. This is related, among other things, to the activation of PI3K→Akt/PKB and ERK MAPK pathways [ 127 ].…”

Tumor Microenvironment Heterogeneity: Challenges and Opportunities

“…It was found that human breast cancer specimens exhibited significant association between mRNA expression levels of MIP-1β and MYO3A and both, whether MIP-1β and MYO3A showed positive correlation with an established molecular determinant of cancer cell invasion, MMP9. Higher expression of these genes correlated with poor survival of breast cancer patients (Baghel et al, 2016). …”

Human omental adipose‐derived stem cells from donors with different body mass index had similar effects on proliferation and migration of endometrial cancer cells in vitro

“…Besides, MIP‐1β critically involved in peripheral monocyte activation and adipose tissue infiltration resulting in an overweight or obese status, which has a higher risk for EC . In addition, Baghel et al . reported that MIP‐1β could enhance the invasive potential of metastatic breast cancer cells.…”