Inhibitory effect of vasoactive intestinal polypeptide (VIP) on experimental liver metastasis by murine colon 26-L5 carcinoma cells.

Abstract:

:We previously reported that vasoactive intestinal polypeptide (VIP) significantly inhibited Matrigel invasion and haptotactic migration of murine colon 26-L5 carcinoma in vitro. To extend our study, we investigated the inhibitory mechanisms of VIP on Matrigel invasion of colon 26-L5 carcinoma, and the effect on metastatic properties of the tumor cells. VIP inhibited the invasion of the tumor cells in a concentration-dependent manner without affecting their growth, and achieved approximately 50% reduction at 10(-6) M. VIP also suppressed cell motility with a similar inhibition rate to the invasion assay. Time course study revealed that the motility was reduced by 40% when the tumor cells were preincubated with 10(-6) M VIP for 3 h. In contrast, 6-h pretreatment with 10(-6) M VIP caused the increased ability of the adhesion to both fibronectin and laminin with a 50% enhancement. A large amount of VIP1 receptor transcripts was expressed in the cells, whereas VIP2 receptor was undetectable, by RT-PCR and subsequent Southern blot hybridization. A specific antagonist for VIP1 receptor reversed the suppressed motility induced by VIP. Cryostat sections showed that the 3-h pretreatment of tumor cells with VIP caused the reduction of the arrest in the livers at 6 h after the tumor inoculation into a portal vein of mice. VIP could prevent the experimental liver metastasis of the tumor cells in a dose-dependent manner. The cells pretreated with 10(-6) M VIP for 3 h also showed the reduced ability of the liver metastasis. These results suggest that VIP could block the invasion and the metastasis of colon 26-L5 carcinoma through suppression of their motility.

journal_name

Oncol Res

journal_title

Oncology research

authors

Ogasawara M,Murata J,Ayukawa K,Saiki I

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

361-70

issue

7

eissn

0965-0407

issn

1555-3906

journal_volume

10

pub_type

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