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Histo-Blood Group A/B versus H Status of Human Carcinoma Cells as Correlated with Haptotactic Cell Motility: Approach with A and B Gene Transfection¹

Department of Pathobiology, University of Washington, and Biomembrane Division, Pacific Northwest Research Foundation, Seattle, Washington 98122

In a search for the molecular basis of ABH status of tumors as correlated with malignancy, we studied various malignancy-related phenotypes of high H/Le^y-expressing tumor cell lines in comparison with phenotypes of the same lines transfected with histo-blood group A or B genes. A and B gene transfectants, prepared independently from different H-active parental cells, showed A or B activity and abolition of H activity. All A and B gene transfectants, regardless of source, were characterized by significantly reduced Matrigel-dependent haptotactic motility. The level of haptotaxis of all transfectants was similar to that of parental cells in the presence of antibodies against human integrin subunits 3, 6, or ß1. These subunits showed high expression of A or B epitope in the A and B gene transfectants. Enhancement versus reduction of malignancy, associated with deletion versus induction of A/B epitopes, may be due in part to enhanced haptotaxis sustained by 3, 6, and ß1 integrin receptors, the activities of which are regulated by H or A/B glycosylation. These phenotypic changes provide a rationale for the deletion of A and B epitopes as one criterion defining human tumor malignancy.

¹ Dedicated to Roger W. Jeanloz on the occasion of his 80th birthday. This study was supported by National Cancer Institute Outstanding Investigator Grant CA42505 (to S. H.).

² Present address: First Department of Surgery, Kyoto Prefectural University of Medicine, Kawara-machi, Kyoto 602, Japan.

³ To whom requests for reprints should be addressed, at Pacific Northwest Research Foundation, 720 Broadway, Seattle, WA 98122. Phone: (206) 726-1222; Fax: (206) 726-1212; E-mail: hakomori@u.washington.edu.

Received 4/28/97. Accepted 6/12/97.

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