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Low E-cadherin and β-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas

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Abstract

This study examined the relationship between the expression of E-cadherin or β-catenin in murine adenocarcinomas and their hematogenous metastatic propensity, assessed by both spontaneous and artificial lung metastasis. Seven different carcinomas, syngeneic to C3Hf/Kam mice were used: 4 mammary carcinomas (MCa-4, MCa-29, MCa-35, and MCa-K), ovarian carcinoma OCa-I, hepatocarcinoma HCa-I, and adenosquamous carcinoma ACa-SG. These tumors vary widely in their ability to spontaneously metastasize to the lung (from 0 to 100% metastatic incidence), and their cells greatly differ in their ability to form artificial lung nodules when injected i.v. Primary tumors in the leg were assessed for E-cadherin and β-catenin expression by western botting. The expression of both proteins showed wide variation among the tumors; however, the expression of E–cadherin correlated well with that of β-catenin. There was significant inverse correlation between the expression of E-cadherin, as well as β-catenin, and the incidence of both spontaneous and artificial lung metastases from these tumors. Spontaneous metastases of highly metastatic HCa-I and moderately metastatic MCa-35 were significantly lower in E-cadherin and β-catenin expression than their corresponding primary tumors were. Thus, the propensity of murine carcinomas for hematogenous spread is highly related to E-cadherin and β-catenin levels in primary tumors. The inverse correlation between the expression of these molecules and spontaneous and artificial metastases implies that tumor cells with low E-cadherin and β-catenin content have increased ability to enter the vascular circulation at the primary tumor site and to colonize distant tissues.

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Akimoto, T., Kawabe, S., Grothey, A. et al. Low E-cadherin and β-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas. Clin Exp Metastasis 17, 171–176 (1999). https://doi.org/10.1023/A:1006670918848

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