Suppression of human bladder cancer growth by increased expression of C-CAM1 gene in an orthotopic model.
Recently, we demonstrated that an immunoglobulin-like cell adhesion molecule, C-CAM, acts as a tumor suppressor in prostate cancer. It is known that C-CAM is expressed in many epithelial cell types. In this study, we tested the possibility that C-CAM may also suppress bladder cancer progression. We used an orthotopic tumor model, which provides a relevant organ condition for examining the interaction between primary tumor cells and their microenvironment; this interaction has a critical impact on the behavior of carcinoma. We constructed a recombinant adenovirus expressing C-CAM1 (an isoform of C-CAM) and infected the 253J B-V cell line, a tumorigenic human bladder carcinoma subline. In vitro, C-CAM1 protein was detected in C-CAM1 adenovirus-infected cells but not in antisense control virus-infected cells, and the levels of expression showed dose dependency. When these cells were injected orthotopically in nude mice, we found that the increased expression of C-CAM1 in the 253J B-V cells repressed the growth of 253J B-V-induced tumors. Taken together, these data indicate that C-CAM1 is a potent tumor suppressor in human bladder cancer.
Kleinerman
D I
DI
Department of Urology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Dinney
C P
CP
Zhang
W W
WW
Lin
S H
SH
Van
N T
NT
Hsieh
J T
JT
D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000502:physiology*; D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000257:Adenoviridae Infections / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006023:Glycoproteins; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D051379:Mice; D008819:Mice, Nude; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
D015703:Antigens, CD; C069847:CD66 antigens; D002272:Carcinoembryonic Antigen; C486183:Ceacam1 protein, mouse; C087701:Ceacam2 protein, mouse; D015815:Cell Adhesion Molecules; D006023:Glycoproteins; D000251:Adenosine Triphosphatases