hMan2c1 transgene promotes tumor progress in mice.
In order to study the biological significance of alpha-mannosidase Man2c1, hMan2c1 transgenic mice were developed. In 113 F0 mice, eight were found to be genomic PCR positive for hMan2c1; 9/20 (45%) F1 mice, 16/21 (76.2%) F2 mice, and 12/14 (85.7%) F3 mice were genomic PCR positive for hMan2c1. RT-PCR demonstrated hMan2c1 mRNA transcription in four of eight transgenic lines. Enzymatic activity on p-nitrophenyl-alpha-D: -mannopyranoside was enhanced in 35# and 54# transgenic mice and real-time RT-PCR showed hMan2c1 mRNA expression in these mice. Reduced Con A binding to splenocytes implied N-glycosylation modification of host proteins by hMan2c1 transgene. hMan2c1 transgene promoted growth, invasion, and metastasis to lung of implanted hepatoma H22 and sarcoma S180. The average weights of H22 and S180 tumors were 3.98 +/- 1.62, 3.29 +/- 0.76, 1.69 +/- 1.09, and 3.19 +/- 0.44, 2.72 +/- 1.38, 0.97 +/- 0.41 g for 35#, 54# transgenic mice and wild type mice (W), respectively, (35# or 54# versus W, paired t-test, P < 0.05). In 35# and 54# mice 5/10 and 3/10 showed lung metastasis of H22 tumor in contrast with 1/10 in W mice. In 35# and 54# mice 1/6 and 2/6 showed lung metastasis of S180 tumor in contrast with 0/6 in W mice. The possible mechanism of the promotion was explored on both humoral and cellular immunity. Reduced antibody response to BSA was observed in transgenic mice, suggesting that specific antibody response to tumor antigens might be suppressed by hMan2c1 transgene. However, NK cytotoxicity in splenocytes was not affected by the transgene.
Xiang
Z G
ZG
Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, China.
Jiang
D D
DD
Liu
Y
Y
Zhang
L F
LF
Zhu
L P
LP
D000818:Animals; D000917:Antibody Formation / Q000235:genetics; D019556:COS Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic / Q000235:genetics; D018450:Disease Progression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology / Q000473:pathology; D008361:Mannosidases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008822:Mice, Transgenic; D009369:Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000378:metabolism / Q000473:pathology; D019076:Transgenes / Q000502:physiology*; D014407:Tumor Cells, Cultured; D019139:Tumor Escape / Q000235:genetics; D043323:alpha-Mannosidase
D008361:Mannosidases; C511245:MAN2C1 protein, human; D043323:alpha-Mannosidase