{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMCAM (also known as CD146 or MUC18) is a multifunctional cell adhesion molecule that plays critical roles in stem cell biology and tissue regeneration. In mesenchymal and hematopoietic stem cell compartments, high MCAM expression is used to prospectively isolate perivascular and multipotent progenitor cells, and its levels correlate with clonogenicity, lineage‐differentiation potential, and even resistance to cellular senescence. These data suggest that MCAM is not only a phenotypic marker for mesenchymal stem/stromal cells but also plays a regulatory role in maintaining “stemness” and supporting niche functions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn vascular biology, MCAM is integral for endothelial cell–cell cohesion and angiogenesis. It acts as a co‐receptor for VEGFR-2 by directly interacting with it, thereby modulating VEGF-induced signaling cascades that include phosphorylation events, activation of downstream kinases, and NF-κB–dependent gene expression. In addition, MCAM is a direct binding partner for extracellular ligands such as Galectin-3, and its soluble form is detectable in plasma—findings that underscore its role in regulating vascular permeability and orchestrating angiogenic responses both in normal and tumor-associated vessels."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of cancer, MCAM is widely implicated as a driver of tumor progression and metastasis. Up-regulation of MCAM has been observed in a variety of malignancies—including melanoma, prostate, ovarian, gastric, and small-cell lung cancers—and correlates with advanced disease, invasive behavior, and chemoresistance. Its ability to modulate cytoskeletal rearrangements (via interactions with ERM proteins and activation of RhoA), promote cell–cell interactions and migration, and cross-talk with signaling pathways such as AKT and noncanonical Wnt underscores its role in the epithelial-to-mesenchymal transition and metastatic dissemination. Furthermore, paracrine effects mediated by MCAM in tumor-associated fibroblasts have been linked to altered hormonal responsiveness in breast cancer, while its expression in circulating tumor cells supports its use as a prognostic marker."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "29"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMCAM is also expressed on specific subsets of immune cells, where it facilitates lymphocyte adhesion and transmigration. For instance, in T lymphocytes—including pathogenic TH17 cells implicated in multiple sclerosis and other inflammatory conditions—MCAM expression marks cells with an enhanced capacity to adhere to and migrate through the blood–brain barrier. Similar adhesion functions have been observed in natural killer cells, further supporting a role for MCAM in immune cell trafficking during inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "30", "end_ref": "33"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, owing to its highly tumor-specific expression and functional contribution to disease progression, MCAM is emerging as a promising diagnostic marker and therapeutic target. In malignant pleural mesothelioma, for example, MCAM distinguishes tumor cells from reactive mesothelial cells and has been exploited for targeted delivery of therapeutic agents. Such findings underscore the potential of MCAM‐based strategies both for improved tumor detection and for the development of novel anti‐metastatic therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "34"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "K E Schwab, C E Gargett "}, {"type": "b", "children": [{"type": "t", "text": "Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/dem265"}], "href": "https://doi.org/10.1093/humrep/dem265"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17872908"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17872908"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Katie C Russell, Donald G Phinney, Michelle R Lacey, et al. 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