Nerve growth factor stimulates MMP-2 expression and activity and increases invasion by human pancreatic cancer cells
Tóm tắt
Pancreatic cancer frequently invades and migrates along neural tissue. Although the exact mechanisms are unknown, perineural invasion negatively impacts prognosis for pancreatic cancer patients. Matrix metalloproteinases (MMPs) are overexpressed in pancreatic cancer and are associated with poor prognosis. We hypothesized that nerve growth factor (NGF) released from neural tissue increases the invasive properties of pancreatic cancer cells. In the present study we investigated the effect of NGF on the expression and activity of MMP-2 in human pancreatic cancer cells. NGF dose dependently increased MMP-2 protein in the culture medium and stimulated MMP-2 gelatinolytic activity. This effect was mediated by specific binding of NGF to its receptor trk A, which was detected on all pancreatic cancer cells, with subsequent activation of the p44/42 MAPK signaling pathway. The NGF-induced increase in MMP-2 expression and activity lead to an enhanced invasion in vitro. These findings support the hypothesis that neurotrophic factors, e.g., NGF, are critically involved in mediating perineural invasion of pancreatic cancer.
Tài liệu tham khảo
Jemal A, Thomas A, Murray T et al. Cancer statistics, 2002. CA Cancer J Clin 2002; 52(1): 23–47.
Hirai I, Kimura W, Ozawa K et al. Perineural invasion in pancreatic cancer. Pancreas 2002; 24(1): 15–25.
Ozaki H, Hiraoka T, Mizumoto R et al. The prognostic significance of lymph node metastasis and intrapancreatic perineural invasion in pancreatic cancer after curative resection. Surg Today 1999; 29(1): 16–22.
Takahashi T, Ishikura H, Motohara T et al. Perineural invasion by ductal adenocarcinoma of the pancreas. J Surg Oncol 1997; 65(3): 164–70.
Ketterer K, Rao S, Friess H et al. Reverse transcription-PCR analysis of lasercaptured cells points to potential paracrine and autocrine actions of neurotrophins in pancreatic cancer. Clin Cancer Res 2003; 9 (14): 5127–36.
Marchetti D, Menter D, Jin L et al. Nerve growth factor effects on human and mouse melanoma cell invasion and heparanase production. Int J Cancer 1993; 55(4): 692–9.
Nicolson GL, Menter DG, Herrmann JL et al. Brain metastasis: Role of trophic, autocrine, and paracrine factors in tumor invasion and colonization of the central nervous system. Curr Top Microbiol Immunol 1996; 213( Pt 2) 89–115.
Sariola H. The neurotrophic factors in non-neuronal tissues. Cell Mol Life Sci 2001; 58(8): 1061–6.
Vidaltamayo R, Mery CM, Angeles-Angeles A et al. Expression of nerve growth factor in human pancreatic beta cells. Growth Factors 2003; 21(3–4): 103–7.
Okada Y, Takeyama H, Sato M et al. Experimental implication of celiac ganglionotropic invasion of pancreatic-cancer cells bearing c-ret proto-oncogene with reference to glial-cell-line-derived neurotrophic factor (GDNF). Int J Cancer 1999; 81(1): 67–73.
Okada Y, Eibl G, Duffy JP et al. Glial cell-derived neurotrophic factor upregulates the expression and activation of matrix metalloproteinase-9 in human pancreatic cancer. Surgery 2003; 134(2): 293–9.
Zhu Z, Kleeff J, Kayed H et al. Nerve growth factor and enhancement of proliferation, invasion, and tumorigenicity of pancreatic cancer cells. Mol Carcinog 2002; 35(3): 138–47.
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.
Cox G, O'Byrne KJ. Matrix metalloproteinases and cancer. Anticancer Res 2001; 21(6B): 4207–19.
Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 2001; 17 463–516.
Gong YL, Xu GM, Huang WD et al. Expression of matrix metalloproteinases and the tissue inhibitors of metalloproteinases and their local invasiveness and metastasis in Chinese human pancreatic cancer. J Surg Oncol 2000; 73(2): 95–9.
Gress TM, Muller-Pillasch F, Lerch MM et al. Expression and insitu localization of genes coding for extracellular matrix proteins and extracellular matrix degrading proteases in pancreatic cancer. Int J Cancer 1995; 62(4): 407–13.
Nagase H. Cell surface activation of progelatinase A (proMMP-2) and cell migration. Cell Res 1998; 8(3): 179–86.
Geldof AA, Van Haarst EP, Newling DW. Neurotrophic factors in prostate and prostatic cancer. Prostate Cancer Prostatic Dis 1998; 1 (5): 236–41.
Dolle L, Yazidi-Belkoura I, Adriaenssens E et al. Nerve growth factor overexpression and autocrine loop in breast cancer cells. Oncogene 2003; 22(36): 5592–601.
Yamamoto H, Itoh F, Iku S et al. Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human pancreatic adenocarcinomas: Clinicopathologic and prognostic significance of matrilysin expression. J Clin Oncol 2001; 19(4): 1118–27.
Yang X, Staren ED, Howard JM et al. Invasiveness and MMP expression in pancreatic carcinoma. J Surg Res 2001; 98(1): 33–9.
Koshiba T, Hosotani R, Wada M et al. Involvement of matrix metalloproteinase-2 activity in invasion and metastasis of pancreatic carcinoma. Cancer 1998; 82(4): 642–50.
Kleiner DE, Stetler-Stevenson WG. Quantitative zymography: Detection of picogram quantities of gelatinases. Anal Biochem 1994; 218 (2): 325–9.
Miknyoczki SJ, Lang D, Huang L et al. Neurotrophins and Trk receptors in human pancreatic ductal adenocarcinoma: Expression patterns and effects on in vitro invasive behavior. Int J Cancer 1999; 81(3): 417–27.