Conditionally immortalized human pancreatic stellate cell lines demonstrate enhanced proliferation and migration in response to IGF-I.

Rosendahl, AnnLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund (author)

Pancreatic stellate cells (PSCs) play a key role in the dense desmoplastic stroma associated with pancreatic ductal adenocarcinoma. Studies on human PSCs have been minimal due to difficulty in maintaining primary PSC in culture. We have generated the first conditionally immortalized human non-tumor (NPSC) and tumor-derived (TPSC) pancreatic stellate cells via transformation with the temperature-sensitive SV40 large T antigen and human telomerase (hTERT). These cells proliferate at 33°C. After transfer to 37°C, the SV40LT is switched off and the cells regain their primary PSC phenotype and growth characteristics. NPSC contained cytoplasmic vitamin A-storing lipid droplets, while both NPSC and TPSC expressed the characteristic markers αSMA, vimentin, desmin and GFAP. Proteome array analysis revealed that of the 55 evaluated proteins, 27 (49%) were upregulated ≥3-fold in TPSC compared to NPSC, including uPA, pentraxin-3, endoglin and endothelin-1. Two insulin-like growth factor binding proteins (IGFBPs) were inversely expressed. Although discordant IGFBP-2 and -3 levels, IGF-I was found to stimulate proliferation of both NPSC and TPSC. Both basal and IGF-I stimulated motility was significantly enhanced in TPSC compared to NPSC. In conclusion, these cells provide a unique resource that will facilitate further study of the active stroma compartment associated with pancreatic cancer.

Gundewar, ChinmayLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-cgu (author)
Said Hilmersson, KatarzynaLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)oft-ksa (author)
Ni, Lan (author)
Saleem, Moin A (author)
Andersson, RolandLund University,Lunds universitet,Kirurgi, Lund,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Surgery (Lund),Section V,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)kir-ran (author)
Kirurgi, LundSektion V (creator_code:org_t)

By the author/editor: Rosendahl, Ann; Gundewar, Chinma ...; Said Hilmersson, ...; Ni, Lan; Saleem, Moin A; Andersson, Rolan ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Surgery

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Cancer and Oncol ...

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