Chromogranin A expression in neoplastic cells affects tumor growth and morphogenesis in mouse models.
Chromogranin A (CgA), a secretory protein expressed by many neuroendocrine cells, has been recognized as a useful tissue and serum marker of neuroendocrine tumors. To investigate the effect of CgA secretion on neoplastic morphogenesis and progression, we have transfected mouse RMA lymphoma and TS/A adenocarcinoma cells with the cDNA encoding human CgA and selected several CgA-positive (secreting) and CgA-negative (nonsecreting) clones. In both models, the growth rate of CgA-positive clones implanted s.c. in nude mice was slower than that of CgA-negative clones. Histological analysis of each RMA tumor showed that CgA-expression was associated with multinodular growth patterns, whereas CgA-negative tumors appeared more compact and similar to wild-type RMA tumors. Moreover, CgA production was associated with increased tumor necrosis. The number of nodules in each RMA tumor correlated with the serum levels of CgA (n = 40, r = 0.537, P = 0.0004). The reduced growth rate of CgA-positive RMA and TS/A tumors was not related to reduced in vitro proliferation or to changes in cell adhesion and shape, suggesting that the mechanism is indirect and host-mediated. These results suggest that abnormal secretion of CgA by neuroendocrine neoplastic cells could affect neoplastic growth and morphogenesis.
Colombo
Barbara
B
Department of Biological and Technological Research, San Raffaele H Scientific Institute, via Olettina 58, 20132 Milan, Italy.
Curnis
Flavio
F
Foglieni
Chiara
C
Monno
Antonella
A
Arrigoni
Gianluigi
G
Corti
Angelo
A
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D002455:Cell Division / Q000502:physiology; D053379:Chromogranin A; D002864:Chromogranins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D006801:Humans; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D014162:Transfection
C506150:CHGA protein, human; D053379:Chromogranin A; D002864:Chromogranins; D018076:DNA, Complementary; C506155:chromogranin A, mouse