Chromogranin A expression in neoplastic cells affects tumor growth and morphogenesis in mouse models

Barbara Colombo, Flavio Curnis, Chiara Foglieni, Antonella Monno, Gianluigi Arrigoni, Angelo Corti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)941-946
Number of pages6
JournalCancer Research
Volume62
Issue number3
Publication statusPublished - Feb 1 2002

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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