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Taking advantage of single-cell and spatial transcriptomic data, we analyzed the cell-type-specific and spatial expression of MMPs in CRCs. Distinct colon cancer-associated fibroblast (CAF) subtypes were found to express different MMP combinations, including MMP1\/3-expressing and MMP11-expressing CAFs. Conversely, myeloid cells (monocytes, macrophages, and dendritic cells) expressed varying levels of the \u201cmyeloid MMPs\u201d 9, 12, and 14, which correlated closely with secretory gene expression. Finally, a small population of cancer cells expressed high levels of MMP7. The MMP7-expressing cancer cells frequently co-expressed MMP1, MMP14, and several Wnt-related genes, consistent with a cancer cell type at high risk of malignancy and metastasis. Spatial transcriptomic data showed MMP expression in discernible clusters driven in part by cell-type localization, including fibroblast-heavy stromal regions and inflammatory cell hubs. Epithelial-rich areas showed subregions of MMP7-expressing cancer cells, including areas where cancer cell and myeloid MMP expression overlap. Tumors showed a wide variation in MMP1-expressing CAFs, a variation reflected in primary CAF cell lines. In vitro, MMP1 expression was a stable phenotype that persisted through multiple rounds of division. MMP1-expressing CAFs were frequently positioned at the stromal interface, suggesting a role in facilitating cell movement across the tumor boundary. Our analysis indicates that cell-type and positional MMP expression varies between tumors and may play a role in determining lesion progression and cancer spread.<\/jats:p>","DOI":"10.64898\/2026.04.17.719089","type":"posted-content","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T16:10:16Z","timestamp":1776787816000},"source":"Crossref","is-referenced-by-count":0,"title":["Integrated Single-Cell and Spatial Profiling of MMP Gene Expression in Colorectal Cancer"],"prefix":"10.64898","author":[{"given":"Nicholas A.","family":"Danese","sequence":"first","affiliation":[{"name":"Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269-3125"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Kurkcu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 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