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A significant factor in this resistance appears to be the dense desmoplastic stroma, which contains various cancer-associated fibroblast (CAF) populations. However, our understanding of the communication between tumor cells and CAFs that contributes to this aggressive malignancy is still developing. Recently, we used an advanced three-dimensional heterospecies, heterospheroid co-culture model to investigate the signaling between human pancreatic tumor Panc1 cells and mouse pancreatic stellate cells (mPSCs) through global expression profiling. Upon discovering that CCN1 was significantly upregulated in Panc1 cells during co-culture, we decided to explore the role of CCN1 using CRISPR-Cas9 knockout technology. Panc1 cells lacking CCN1 showed reduced differentiation and decreased sensitivity to gemcitabine, primarily due to lower expression of genes involved in gemcitabine transport and metabolism. Additionally, we observed that stimulation with TGF-\u03b21 and lysophosphatidic acid increased CCN1 expression in Panc1 cells and induced a shift in mPSCs towards a more myofibroblastic CAF-like phenotype.<\/jats:p>","DOI":"10.3390\/ijms25179369","type":"journal-article","created":{"date-parts":[[2024,8,29]],"date-time":"2024-08-29T11:12:13Z","timestamp":1724929933000},"page":"9369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Crosstalk Analysis between mPSCs and Panc1 Cells Identifies CCN1 as a Positive Regulator of Gemcitabine Sensitivity in Pancreatic Cancer Cells"],"prefix":"10.3390","volume":"25","author":[{"given":"Beate","family":"G\u00fcndel","sequence":"first","affiliation":[{"name":"Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Pf\u00fctzenreuter","sequence":"additional","affiliation":[{"name":"Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5575-8850","authenticated-orcid":false,"given":"Veronika","family":"Engelsberger","sequence":"additional","affiliation":[{"name":"Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7647-198X","authenticated-orcid":false,"given":"J.-Matthias","family":"L\u00f6hr","sequence":"additional","affiliation":[{"name":"Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2782-585X","authenticated-orcid":false,"given":"Rainer","family":"Heuchel","sequence":"additional","affiliation":[{"name":"Pancreas Cancer Research Lab, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, SE 141 86 Huddinge, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. 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