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Gastrin-releasing Peptide: In Vivo and in Vitro Growth Effects on an Acinar Pancreatic Carcinoma

INSERM U.61, Biologie Cellulaire et Physiopathologie Digestive, 3, avenue Molière, 67200 Strasbourg, France

The mammalian gastrin-releasing-peptide (GRP) and its structural amphibian analogue, bombesin, are known to be trophic factors for the normal exocrine pancreas. This work investigates the possible role of GRP in the growth of an acinar pancreatic cancer transplanted to the rat and in primary tumor cell cultures. Moreover, this adenocarcinoma was tested for its content of specific bombesin/GRP receptors by using autoradiographic technics and in vitro binding assays with tumor cells.

In Lewis rats bearing the pancreatic carcinoma transplanted s.c. in the scapular region, chronic administration of GRP at the dose 30 µg/kg/day for 15 successive days significantly increased the tumor volume, the final tumor weight, and amylase, protein, RNA and DNA contents. Autoradiographic studies showed that tumor tissue was GRP receptor positive with a high density. The biochemical characterization indicated that receptor positive tumor tissue had saturable and high affinity receptors with pharmacological specificity for GRP and its bioactive analogues. In primary tumor cell cultures, GRP increased the incorporation of [³H] thymidine in DNA in a dose- and time-dependent manner. There was a good correlation between the ability of GRP and its COOH terminal analogues to elicit DNA synthesis and their affinity for ¹²⁵I-GRP binding sites.

These results from in vivo and in vitro experiments demonstrated that GRP induces growth of pancreatic carcinoma by acting directly on specific membrane receptors present on the tumor cells.

¹ To whom requests for reprints should be addressed.

Received 12/26/91. Accepted 4/24/92.

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