Cancer-associated stromal fibroblasts promote pancreatic tumor progression

Rosa F. Hwang, Todd Moore, Thiruvengadam Arumugam, Vijaya Ramachandran, Keith D. Amos, Armando Rivera, Baoan D Ji, Douglas B. Evans, Craig D. Logsdon

Research output: Contribution to journalArticle

662 Citations (Scopus)

Abstract

Pancreatic adenocarcinoma is characterized by a dense background of tumor associated stroma originating from abundant pancreatic stellate cells. The aim of this study was to determine the effect of human pancreatic stellate cells (HPSC) on pancreatic tumor progression. HPSCs were isolated from resected pancreatic adenocarcinoma samples and immortalized with telomerase and SV40 large T antigen. Effects of HPSC conditioned medium (HPSC-CM) on in vitro proliferation, migration, invasion, soft-agar colony formation, and survival in the presence of gemcitabine or radiation therapy were measured in two pancreatic cancer cell lines. The effects of HPSCs on tumors were examined in an orthotopic murine model of pancreatic cancer by co-injecting them with cancer cells and analyzing growth and metastasis. HPSC-CM dose-dependently increased BxPC3 and Panc1 tumor cell proliferation, migration, invasion, and colony formation. Furthermore, gemcitabine and radiation therapy were less effective in tumor cells treated with HPSC-CM. HPSC-CM activated the mitogen-activated protein kinase and Akt pathways in tumor cells. Co-injection of tumor cells with HPSCs in an orthotopic model resulted in increased primary tumor incidence, size, and metastasis, which corresponded with the proportion of HPSCs. HPSCs produce soluble factors that stimulate signaling pathways related to proliferation and survival of pancreatic cancer cells, and the presence of HPSCs in tumors increases the growth and metastasis of these cells. These data indicate that stellate cells have an important role in supporting and promoting pancreatic cancer. Identification of HPSC-derived factors may lead to novel stroma-targeted therapies for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)918-926
Number of pages9
JournalCancer Research
Volume68
Issue number3
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

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Pancreatic Stellate Cells
Pancreatic Neoplasms
Neoplasms
gemcitabine
Neoplasm Metastasis
Adenocarcinoma
Radiotherapy
Cancer-Associated Fibroblasts
Polyomavirus Transforming Antigens
Forensic Anthropology
Survival
Telomerase
Viral Tumor Antigens
Conditioned Culture Medium
Growth
Mitogen-Activated Protein Kinases
Agar
Cell Movement
Cell Proliferation
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hwang, R. F., Moore, T., Arumugam, T., Ramachandran, V., Amos, K. D., Rivera, A., ... Logsdon, C. D. (2008). Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Research, 68(3), 918-926. https://doi.org/10.1158/0008-5472.CAN-07-5714

Cancer-associated stromal fibroblasts promote pancreatic tumor progression. / Hwang, Rosa F.; Moore, Todd; Arumugam, Thiruvengadam; Ramachandran, Vijaya; Amos, Keith D.; Rivera, Armando; Ji, Baoan D; Evans, Douglas B.; Logsdon, Craig D.

In: Cancer Research, Vol. 68, No. 3, 01.02.2008, p. 918-926.

Research output: Contribution to journalArticle

Hwang, RF, Moore, T, Arumugam, T, Ramachandran, V, Amos, KD, Rivera, A, Ji, BD, Evans, DB & Logsdon, CD 2008, 'Cancer-associated stromal fibroblasts promote pancreatic tumor progression', Cancer Research, vol. 68, no. 3, pp. 918-926. https://doi.org/10.1158/0008-5472.CAN-07-5714
Hwang RF, Moore T, Arumugam T, Ramachandran V, Amos KD, Rivera A et al. Cancer-associated stromal fibroblasts promote pancreatic tumor progression. Cancer Research. 2008 Feb 1;68(3):918-926. https://doi.org/10.1158/0008-5472.CAN-07-5714
Hwang, Rosa F. ; Moore, Todd ; Arumugam, Thiruvengadam ; Ramachandran, Vijaya ; Amos, Keith D. ; Rivera, Armando ; Ji, Baoan D ; Evans, Douglas B. ; Logsdon, Craig D. / Cancer-associated stromal fibroblasts promote pancreatic tumor progression. In: Cancer Research. 2008 ; Vol. 68, No. 3. pp. 918-926.
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