Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2001 Dec;7(6):816-20.
doi: 10.3748/wjg.v7.i6.816.

SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma

Affiliations

SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma

Q Xie et al. World J Gastroenterol. 2001 Dec.

Abstract

Aim: To explore the role of SF/HGF-Met autocrine and paracrine in metastasis of hepatocellular carcinoma (HCC).

Methods: SF/HGF and c-met transcription and protein expression in HCC were examined by RT-PCR and Western Blot in 4 HCC cell lines, including HepG2, Hep3B, SMMC7721 and MHCC-1, the last cell line had a higher potential of metastasis. sf/hgf cDNA was transfected by the method of Lipofectin into SMMC7721. SF/HGF and c-met antibody were used to stimulate and block SF/HGF-c-met signal transduction. Cell morphology, mobility, and proliferation were respectively compared by microscopic observation, wound healing assay and cell growth curve.

Results: HCC malignancy appeared to be relative to its met-SF/HGF expression. In MHCC-1, c-met expression was much stronger than that in other cell lines with lower potential of metastasis and only SF/HGF autocrine existed in MHCC-1. After sf/hgf cDNA transfection or conditioned medium of MHCC-1 stimulation, SMMC7721 changed into elongated morphology, and the abilities of proliferation (P < 0.05) and mobility increased. Such bio-activity could be blocked by c-met antibody (P < 0.05).

Conclusion: The system of SF/HGF-c-met autocrine and paracrine played an important role in development and metastasis potential of HCC. Inhibition of SF/HGF-c-met signal transduction system may reduce the growth and metastasis of HCC.

PubMed Disclaimer

Figures

Figure 1
Figure 1
SF/HGF and c-met expression in HCC cell lines. A: c-met transcription; B: SF/HGF transcription 1: Mark; 2: MHCC-1; 3: HepG2; 4: Hep3B; 5: SMMC7721; 6: pBS7.3; C: c-met protein expression; D: SF/HGF protein expression (1: Mark; 2: SMMC7721; 3: Hep3B; 4: HepG2; 5: MHCC-1).
Figure 2
Figure 2
A: cell morphology comparison. × 400. Left: SMMC7721; Right: SF7721; Up: Control at “0” time ; Left down: SMMC7721 at 16 h after wound healing; Right down: SF7721 at 16 h after wound helaing; B: Cell morphology comparison × 400; C: Cell growth curve before and after gene transfection.
Figure 3
Figure 3
C-met inhibition assay.

Similar articles

Cited by

References

    1. Cao B, Su Y, Oskarsson M, Zhao P, Kort EJ, Fisher RJ, Wang LM, Vande Woude GF. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc Natl Acad Sci USA. 2001;98:7443–7448. - PMC - PubMed
    1. Atabey N, Gao Y, Yao ZJ, Breckenridge D, Soon L, Soriano JV, Burke TR, Bottaro DP. Potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion and branching morphogenesis by antagonists of Grb2 Src homology 2 domain interactions. J Biol Chem. 2001;276:14308–14314. - PubMed
    1. Furge KA, Zhang YW, Vande Woude GF. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene. 2000;19:5582–5589. - PubMed
    1. Shaharabany M, Abramovitch R, Kushnir T, Tsarfaty G, Ravid-Megido M, Horev J, Ron R, Itzchak Y, Tsarfaty I. In vivo molecular imaging of met tyrosine kinase growth factor receptor activity in normal organs and breast tumors. Cancer Res. 2001;61:4873–4878. - PubMed
    1. Boccaccio C, Andò M, Tamagnone L, Bardelli A, Michieli P, Battistini C, Comoglio PM. Induction of epithelial tubules by growth factor HGF depends on the STAT pathway. Nature. 1998;391:285–288. - PubMed

Publication types

MeSH terms

Substances