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Bombesin Stimulates Adhesion, Spreading, Lamellipodia Formation, and Proliferation in the Human Colon Carcinoma Isreco1 Cell Line¹

Institut National de la Santé et de la Recherche Médicale U45, Hôpital E. Herriot, 69437 Lyon Cedex 3, France [J. C. S., E. N-G., J. C. C., J. A., J. A. C.]; Department of Experimental Pathology, Swiss Institute for Cancer Research (Isrec), 1066 Epalinges, Switzerland [B. S.]; and Tulane University, New Orleans, Louisiana 70112-2699 [D. H. C.]

The neuropeptide bombesin and its mammalian homologue, gastrin-releasing peptide (GRP), enhance proliferation in some but not all human tumor cell lines. The pathophysiological relevance of the bombesin/GRP receptor (GRP-R), which is expressed in 30% of human colon tumor cell lines and in 24–40% of native tumors, has not been clearly assessed at this time. We studied the effects of bombesin in the recently characterized human colon carcinoma Isreco1 cell line. Competitive reverse transcription-PCR showed a high GRP-R mRNA level in Isreco1 cells, and binding studies confirmed the expression of bombesin/GRP-subtype receptors (K_d = 0.42 nM; B_max = 18,000 sites/cell). Exposure to bombesin resulted in an increase of intracellular calcium concentrations. Bombesin (1 nM) induced cell spreading at 24 h (21.7 ± 1.6% versus 6.4 ± 0.8% in control cells; P < 0.01) and markedly increased the formation of lamellipodia. In addition, adhesion of Isreco1 cells to collagen I-coated culture dishes was stimulated in the presence of 1 nM bombesin (69 ± 6% versus 42 ± 1% in control cells; P < 0.01). Finally, bombesin significantly increased [³H]thymidine uptake by Isreco1 cells in a dose-dependent manner, with a first significant response at 0.1 nM and a maximal effect at 100 nM bombesin (192.2 ± 9.7% of control). These results clearly indicate that bombesin exerts morphological, adhesive, and proliferative effects on Isreco1 cells, suggesting that expression of the bombesin/GRP-R may contribute to the malignant properties of colon carcinoma cells.

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