TY - JOUR
T1 - Low E-cadherin and β-catenin expression correlates with increased spontaneous and artificial lung metastases of murine carcinomas
AU - Akimoto, Tetsuo
AU - Kawabe, Shinichiro
AU - Grothey, Axel
AU - Milas, Luka
N1 - Funding Information:
This work was supported by NIH Research Grants CA-06294 and CA-16672. We are grateful to Lane Watkins and his staff for the supply and care of the mice used in this study. Animals used in this study were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current regulations and standards of the United States Department of Agriculture and Department of Health and Human Services. We wish to thank Patricia Norfleet and Glynda Smith for their assistance in the preparation of this manuscript. Also, we wish to thank Pierre D. McCrea, Ph.D., Department of Biochemistry and Molecular Biology, M. D. Anderson Cancer Center, Houston, Texas, for helpful discussions.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
KW - E-cadherin
KW - Hematogenous metastasis
KW - Mouse tumor
KW - β-catenin
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U2 - 10.1023/A:1006670918848
DO - 10.1023/A:1006670918848
M3 - Article
C2 - 10411110
AN - SCOPUS:0032791603
SN - 0262-0898
VL - 17
SP - 171
EP - 176
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 2
ER -