Differential gene expression in metastasizing cells shed from kidney tumors
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Differential gene expression in metastasizing cells shed from kidney tumors. / Bockhorn, Maximilian; Roberge, Sylvie; Sousa, Cristina; Jain, Rakesh K; Munn, Lance L.
In: CANCER RES, Vol. 64, No. 7, 01.04.2004, p. 2469-73.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Differential gene expression in metastasizing cells shed from kidney tumors
AU - Bockhorn, Maximilian
AU - Roberge, Sylvie
AU - Sousa, Cristina
AU - Jain, Rakesh K
AU - Munn, Lance L
PY - 2004/4/1
Y1 - 2004/4/1
N2 - We developed a novel orthotopic mouse tumor model of renal cell carcinoma to collect and characterize cells spontaneously shed from SN12C (renal cell carcinoma) and SN12L1 (high metastatic variant of SN12C) tumors grown in kidneys of severe combined immunodeficient mice. Viability of the shed cell population was greater for SN12L1 tumors (25%) compared with SN12C tumors (11%, P < 0.05). Gene array analysis of 23 genes involved in metastasis showed that CD44, alpha3 integrin, and caveolin were down-regulated in the shed tumor cells compared with their primary counterparts, and blocking alpha3 integrin or CD44 function inhibited attachment and migration of both cell lines. These results suggest that cohesion of the cells within the primary tumor mediated by CD44 and alpha3 integrins hinders metastasis and that shedding is a passive process not necessarily mediated by cell migration in these tumors. Furthermore, resistance to apoptosis may enhance metastasis in the higher metastatic tumor.
AB - We developed a novel orthotopic mouse tumor model of renal cell carcinoma to collect and characterize cells spontaneously shed from SN12C (renal cell carcinoma) and SN12L1 (high metastatic variant of SN12C) tumors grown in kidneys of severe combined immunodeficient mice. Viability of the shed cell population was greater for SN12L1 tumors (25%) compared with SN12C tumors (11%, P < 0.05). Gene array analysis of 23 genes involved in metastasis showed that CD44, alpha3 integrin, and caveolin were down-regulated in the shed tumor cells compared with their primary counterparts, and blocking alpha3 integrin or CD44 function inhibited attachment and migration of both cell lines. These results suggest that cohesion of the cells within the primary tumor mediated by CD44 and alpha3 integrins hinders metastasis and that shedding is a passive process not necessarily mediated by cell migration in these tumors. Furthermore, resistance to apoptosis may enhance metastasis in the higher metastatic tumor.
KW - Animals
KW - Antigens, CD44
KW - Apoptosis
KW - Carcinoma, Renal Cell
KW - Caveolin 1
KW - Caveolins
KW - Down-Regulation
KW - Gene Expression Regulation, Neoplastic
KW - Humans
KW - Integrin alpha3
KW - Kidney Neoplasms
KW - Male
KW - Mice
KW - Mice, SCID
KW - Neoplasm Metastasis
KW - Neoplasm Transplantation
KW - Transplantation, Heterologous
M3 - SCORING: Journal article
C2 - 15059900
VL - 64
SP - 2469
EP - 2473
JO - CANCER RES
JF - CANCER RES
SN - 0008-5472
IS - 7
ER -