Cell-Adhesion Molecules May Be Key to Controlling Metastases in Breast Cancer

NEW YORK--Cell-adhesion molecules (proteins on the cell surfacethat interlock with those of other cells) appear to play an importantrole in checking tumor metastasis, says Dr. Rachel Hazan, a biochemistat Memorial Sloan-Kettering Cancer Center.

Tumor cells may lose their adhesive properties and detach fromthe primary tumor, allowing them to travel through the lymph systemand bloodstream to other organs (see illustration ).

"Metastasis is, of course, the major cause of death frombreast cancer," said Dr. Hazan, who works in Memorial's BreastCancer Research Laboratory, headed by Breast Service Chief PatrickI. Borgen. "So understanding how metasta-sis happens andlearning to control it could have enormous advantages for thesepatients."

Studies at Memorial Sloan-Kettering and elsewhere have shown thatin metastasizing cancer cells, the E-cadherin protein, an essentialadhesion molecule, is often absent or dysfunctional. Researchby Dr. Hazan and her colleagues is focusing on catenins, proteinswithin cells that regulate the functioning of adhesion molecules.

Beta-catenin, for example, appears to regulate the functioningof E-cadherin, and Dr. Hazan is studying how beta-catenin interactswith enzymes linked to cancer progression.

Using Memorial Sloan-Kettering's vast tumor bank, Dr. Hazan isattempting to correlate the levels of E-cadherin present in breastcancer tissue samples with clinical and pathological data. Todate, her work has corroborated other research showing that E-cadherinlevels decrease as breast cancer progresses.

New therapies that could result from this early research wouldaim to restore adhesive properties to tumor cells to prevent metastasis.

"By understanding the function of adhesion molecules, wecan begin to think about new therapeutic tools. If we can learnhow to control metastasis, then cancer won't be such a tragicdisease."