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Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells.
Clin Cancer Res 2001; 7(1):105-12CC

Abstract

Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription-PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa-2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time-dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy.

Authors+Show Affiliations

Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11205897

Citation

Zhu, Z W., et al. "Nerve Growth Factor Exerts Differential Effects On the Growth of Human Pancreatic Cancer Cells." Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, vol. 7, no. 1, 2001, pp. 105-12.
Zhu ZW, Friess H, Wang L, et al. Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells. Clin Cancer Res. 2001;7(1):105-12.
Zhu, Z. W., Friess, H., Wang, L., Bogardus, T., Korc, M., Kleeff, J., & Büchler, M. W. (2001). Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells. Clinical Cancer Research : an Official Journal of the American Association for Cancer Research, 7(1), pp. 105-12.
Zhu ZW, et al. Nerve Growth Factor Exerts Differential Effects On the Growth of Human Pancreatic Cancer Cells. Clin Cancer Res. 2001;7(1):105-12. PubMed PMID: 11205897.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nerve growth factor exerts differential effects on the growth of human pancreatic cancer cells. AU - Zhu,Z W, AU - Friess,H, AU - Wang,L, AU - Bogardus,T, AU - Korc,M, AU - Kleeff,J, AU - Büchler,M W, PY - 2001/2/24/pubmed PY - 2001/3/27/medline PY - 2001/2/24/entrez SP - 105 EP - 12 JF - Clinical cancer research : an official journal of the American Association for Cancer Research JO - Clin. Cancer Res. VL - 7 IS - 1 N2 - Nerve growth factor (NGF) exerts both stimulatory and inhibitory effects on neuronal and certain nonneuronal tumors with the effect based on the type of tumor. We investigated NGF and its receptors (TrkA and p75) in pancreatic cancer cells (PANC-1, MIA-PaCa-2, CAPAN-1, ASPC-1, and T3M4) by reverse transcription-PCR, Western blot analysis, NGF ELISA, and growth assays. NGF mRNA was present at comparable levels in all five pancreatic cancer cell lines. TrkA expression was relatively high in PANC-1 and MIA-PaCa-2 cells and low in CAPAN-1, ASPC-1, and T3M4 cells. p75 expression was high in PANC-1, MIA-PaCa-2, and T3M4 cells, moderate in CAPAN-1, and low in ASPC-1 cells. By ELISA assay, the intracellular NGF content in all cell lines was approximately 40 pg/10(6) cells. NGF content increased significantly in PANC-1 and MIA-PaCa-2 cells when these cells were cultured with serum-free media, whereas there was no change in the other cancer cell lines. PANC-1 and MIA-PaCa-2 cells but not the other cell lines released NGF in the culture media. Exogenous NGF stimulated the growth of PANC-1 and MIA-PaCa-2 cells, inhibited the growth of T3M4 and CAPAN-1 cells in a dose- and time-dependent manner, and did not affect the growth of ASPC-1 cells. NGF led to the phosphorylation of TrkA, mitogen-activated protein kinase (MAPK), and p38 MAPK but not stress-activated protein kinase/c-Jun NH2-terminal kinase in PANC-1 and MIA-PaCa-2 cells. In contrast, in the other pancreatic cancer cell lines none of these kinases were phosphorylated by NGF. In conclusion, the effects of NGF on pancreatic cancer cell growth are dependent on the expression levels and the balance of its TrkA and p75 receptors. NGF-induced pancreatic cancer cell growth seems to be mediated through the phosphorylation of TrkA and subsequently via MAPK. These results point to a previously unknown autocrine/paracrine pathway in pancreatic cancer, suggesting that NGF-TrkA interactions are important factors influencing cell growth and spread in this malignancy. SN - 1078-0432 UR - https://www.unboundmedicine.com/medline/citation/11205897/Nerve_growth_factor_exerts_differential_effects_on_the_growth_of_human_pancreatic_cancer_cells_ L2 - http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=11205897 DB - PRIME DP - Unbound Medicine ER -