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From nascent intraductal neoplasms to disseminated metastatic disease, several levels of evolutionary adaptations and selections occur. Here, we focus on one example of such an adaptation mechanism, namely, \u201cniche construction\u201d promoted by adaptation to acidosis, which is a metabolic adaptation to the early harsh environment in intraductal neoplasms. The avascular characteristics of ductal carcinoma in situ (DCIS) make the periluminal volume profoundly acidic, and cancer cells must adapt to this to survive. Based on discovery proteomics, we hypothesized that a component of acid adaptation involves production of collagen by pre\u2010cancer cells that remodels the extracellular matrix (ECM) and stabilizes cells under acid stress. The proteomic data were surprising as collagen production and deposition are commonly believed to be the responsibility of mesenchymally derived fibroblasts, and not cells of epithelial origin. Subsequent experiments in 3D culture, spinning disk and second harmonic generation microscopy of DCIS lesions in patients\u2019 samples are concordant. Collagen production assay by acid\u2010adapted cells in vitro demonstrated that the mechanism of induction involves the RAS and SMAD pathways. Secretome analyses show upregulation of ECM remodeling enzymes such as TGM2 and LOXL2 that are collagen crosslinkers. These data strongly indicate that acidosis in incipient cancers induces collagen production by cancer cells and support the hypothesis that this adaptation initiates a tumor\u2010permissive microenvironment promoting survival and growth of nascent cancers.<\/jats:p>","DOI":"10.1111\/eva.13075","type":"journal-article","created":{"date-parts":[[2020,7,22]],"date-time":"2020-07-22T17:19:09Z","timestamp":1595438349000},"page":"2689-2703","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Collagen production and niche engineering: A novel strategy for cancer cells to survive acidosis in DCIS and evolve"],"prefix":"10.1111","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7744-6161","authenticated-orcid":false,"given":"Mehdi","family":"Damaghi","sequence":"first","affiliation":[{"name":"Department of Cancer Physiology Moffitt Cancer Center and Research Institute Tampa FL USA"},{"name":"Department of Oncologic Sciences Morsani College of Medicine University of South Florida Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetoshi","family":"Mori","sequence":"additional","affiliation":[{"name":"Center for Immunology and Infectious Diseases Comprehensive Cancer Center Department of Pathology and Laboratory Medicine School of Medicine University of California, Davis Sacramento CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Cancer Physiology Moffitt Cancer Center and Research Institute Tampa FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Cancer Physiology Moffitt Cancer Center and Research Institute Tampa FL 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