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Salivary carcinoma in HER‐2/neu transgenic male mice: An angiogenic switch is not required for tumor onset and progression
Author(s) -
Diodoro Maria Grazia,
Di Carlo Emma,
Zappacosta Roberta,
Iezzi Manuela,
Coletti Anna,
Modesti Andrea,
D'Antuono Tommaso,
Forni Guido,
Musiani Piero
Publication year - 2000
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/1097-0215(20001101)88:3<329::aid-ijc2>3.0.co;2-5
Subject(s) - genetically modified mouse , carcinoma , transgene , tumor progression , cancer research , angiogenesis , medicine , biology , pathology , endocrinology , oncology , cancer , gene , genetics
Morphologic examinations of salivary gland neoplasias arising in male BALB/c (H‐2 d ) mice carrying the activated HER‐2/neu (BALB‐NeuT) indicate that expression of the oncogene product in the ductal‐acinar structures results in a very human‐like acinic cell adenocarcinoma with a smoldering course and infrequent metastatization. Typical and then atypical hyperplasia of ducts and acini preceded the rise of salivary tumors that originated from the confluence of multiple ductal hyperplastic foci, while hyperplastic acini behaved as an abortive preneoplastic lesion. The vascular network in normal, hyperplastic and neoplastic salivary tissue was analysed to see whether activation of the angiogenic process is essential in salivary gland carcinogenesis. Immunostaining with anti‐endothelial cells (anti‐CD31), anti‐β 3 integrin and anti‐laminin antibodies revealed that microvessel density was significantly higher in normal and hyperplastic than in neoplastic tissue, in which no signs of new vessel sprouting were found. Assessment of angiogenic factor expression indicates a low presence of VEGF in normal, hyperplastic and neoplastic epithelium, while bFGF was preferentially produced but not exported by neoplastic cells and remained in a cell‐associated form. Our data suggest that normal salivary gland vascularization is able to support tumor onset and development with no need for an angiogenic switch. Int. J. Cancer 88:329–335, 2000. © 2000 Wiley‐Liss, Inc.