Mcam, also known as Melanoma cell adhesion molecule (CD146/MUC18), is an adhesion molecule of the immunoglobulin superfamily. It plays roles in cell-cell adhesion and is involved in multiple biological processes, especially angiogenesis, and is associated with the Wnt signaling pathway [3]. Genetic models, such as knockout mice, are valuable for studying its functions.

In mammary gland development, Mcam knockout in mice increases the clonogenicity and regenerative capacity of mammary gland epithelial cells (MECs). It promotes MEC proliferation, differentiation, and ductal morphogenesis by recruiting and polarizing macrophages through the Il4-Stat6 axis, which in turn promotes secretion of the non-canonical Wnt ligand Wnt5a and its binding to the receptor Ryk [1]. In colorectal carcinogenesis, stromal Mcam knockout in mice attenuates orthotopically injected colorectal tumoroid growth and improves survival by decreasing tumor-associated macrophage recruitment. Fibroblast MCAM interacts with interleukin-1 receptor 1 to augment nuclear factor κB-IL34/CCL8 signaling that promotes macrophage chemotaxis [2].

In conclusion, Mcam is crucial in regulating cell-related functions in processes like mammary gland development and colorectal carcinogenesis. Gene knockout mouse models have revealed its role in promoting or inhibiting cell growth and immune cell recruitment in these contexts, providing insights into potential therapeutic targets for related diseases.

References:

1. Yang, Xing, Xu, Haibo, Yang, Xu, Hou, Zongliu, Jiao, Baowei. 2024. Mcam inhibits macrophage-mediated development of mammary gland through non-canonical Wnt signaling. In Nature communications, 15, 36. doi:10.1038/s41467-023-44338-0. https://pubmed.ncbi.nlm.nih.gov/38167296/

2. Kobayashi, Hiroki, Gieniec, Krystyna A, Lannagan, Tamsin R M, Woods, Susan L, Worthley, Daniel L. 2021. The Origin and Contribution of Cancer-Associated Fibroblasts in Colorectal Carcinogenesis. In Gastroenterology, 162, 890-906. doi:10.1053/j.gastro.2021.11.037. https://pubmed.ncbi.nlm.nih.gov/34883119/

3. Joshkon, Ahmad, Heim, Xavier, Dubrou, Cléa, Bardin, Nathalie, Blot-Chabaud, Marcel. 2020. Role of CD146 (MCAM) in Physiological and Pathological Angiogenesis-Contribution of New Antibodies for Therapy. In Biomedicines, 8, . doi:10.3390/biomedicines8120633. https://pubmed.ncbi.nlm.nih.gov/33352759/