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Loss of H-Cadherin Protein Expression in Human Non-Small Cell Lung Cancer Is Associated with Tumorigenicity¹

Kaplan Comprehensive Cancer Center [Y. Z., Y. D., J. G., R. P-S.], New York University School of Medicine, New York, New York 10016, and Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School and Harvard Institutes of Medicine, Boston, Massachusetts 02115 [S. W. L.]

Abnormalities in the H-cadherin gene have been described in several human cancers. However, their biological significance remains undetermined. To investigate the role of H-cadherin in non-small cell lung cancer (NSCLC), a chimera H-cadherin-green fluorescent protein (GFP) expressed in Cos-7 cells was used to identify an anti-H- cadherin antibody, HCD-1. Western blot analysis was performed in six NSCLC cell lines and 35 pairs of primary NSCLC tumors and nonmalignant lung tissue obtained from surgical resections using HCD-1. Loss of H-cadherin expression was seen in five (83%) of the six NSCLC cell lines, whereas loss of E-cadherin was seen in three (50%) of the six. H-cadherin expression was lost in 15 (43%) of 35 NSCLC surgical tumor specimens, whereas E-cadherin expression was lost in 6 (17%) of 35. H-cadherin was expressed in all of the nonmalignant lung tissue from all of the surgical specimens. Fourteen of 35 tumors were heterotransplanted s.c. in nude mice. Tumorigenicity in nude mice was associated with both loss of H-cadherin expression (P = 0.03) and loss of E-cadherin expression (P = 0.05). Loss of H-cadherin was also associated with a more advanced local tumor growth, although the difference was not significant. The results indicate that loss of H-cadherin is frequent in human NSCLC and suggest that it facilitates the implantation and local growth of human NSCLC tumors.

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