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Effect of Cancer-related and Drug-induced Alterations in Surface Carbohydrates on the Invasive Capacity of Mouse and Rat Cells¹

Division of Cell Biology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Huis, 121 Plesmanlaan, 1066 CX Amsterdam, the Netherlands [J. G. M. B., D. C. C. S., L. A. S., H. v. R., J. G. C.], and Laboratory of Experimental Cancerology, Department of Radiotherapy and Nuclear Medicine, University Hospital, 185 De Pintelaan, B-9000 Ghent, Belgium [E. A. B., M. M. K. M.]

The effect of alterations in cell surface carbohydrates on invasion of mouse and rat cells into embryonic chick heart fragments in organ culture was studied. Matching pairs of malignant and nonmalignant cells, including all categories of carcinogenic induction (i.e., viral, chemical, or oncogenic), were compared for their alterations in cell surface carbohydrates and invasive behavior. Glycopeptides derived from the surface of malignant cells expressed cancer-related changes in carbohydrate composition, demonstrated by gel filtration chromatography as a shift in size distribution in comparison with those from nonmalignant counterparts. This phenotypic property strictly correlated with the acquisition of the invasive capacity. Morphological transformation of cells without simultaneous alteration in surface carbohydrates was, however, insufficient for invasion.

To test the possible mechanistic role of altered surface carbohydrates in the invasive capacity of cells, the surface molecules of noninvasive cells were modified by incubation with an alkyl-lysophospholipid (racemic 1-O-octadecyl-2-O-methyl glycero-3-phosphocholine). Alkyl-lysophospholipid induced an increase in surface sialylation resembling the changes found in malignant and invasive cells. After pretreatment with alkyl-lysophospholipid, morphologically transformed but nonmalignant and noninvasive cells became able to invade chick heart tissue.

These findings indicate that alterations in cell surface carbohydrates, induced by entirely different mechanisms, endowed cells with invasive capacity.

¹ Supported by grants from the Netherlands Cancer Foundation, Koningin Wilhelmina Fonds (NKI-KWF 84-16), Amsterdam, the Netherlands; from the Nationaal Fonds voor Wetenschappelijk Onderzoek (20.093 and 39.000.983); and from NAVO and Belgisch werk tegen Kanker, Brussels, Belgium.

² To whom requests for reprints should be addressed.

³ Present address: Laboratoria Birstol Benelux, 185-187 Terhulpesesteenweg, 1170 Brussels, Belgium.

Received 12/26/85. Revised 3/24/86. Accepted 4/17/86.

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