Elsevier

Neoplasia

Volume 6, Issue 6, November–December 2004, Pages 768-776
Neoplasia

Early Neoplastic Progression Is Complement Independent

https://doi.org/10.1593/neo.04250Get rights and content
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open access

Abstract

Infiltration of leukocytes into premalignant tissue is a common feature of many epithelial neoplasms and is thought to contribute to cancer development. However, the molecular and cellular regulatory mechanisms underlying activation of innate host responses to enhanced neoplastic cell proliferation are largely unknown. Considering the importance of the complement system in regulating inflammation during acute pathologic tissue remodeling, we examined the functional significance of complement component 3 (C3) as a regulator of inflammatory cell infiltration and activation during malignant progression by using a transgenic mouse model of multistage epithelial carcinogenesis, e.g., HPV16 mice. Whereas abundant deposition of C3 is a characteristic feature of premalignant hyperplasias and dysplasias coincident with leukocyte infiltration in neoplastic tissue, genetic elimination of C3 neither affects inflammatory cell recruitment toward neoplastic skin nor impacts responding pathways downstream of inflammatory cell activation, e.g., keratinocyte hyperproliferation or angiogenesis. Taken together, these data suggest that complementindependent pathways are critical for leukocyte recruitment into neoplastic tissue and leukocytemediated potentiation of tumorigenesis.

Keywords

Cancer
inflammation
complement
immunity
angiogenesis

Abbreviations

BrdU
bromodeoxyuridine
CAE
chloroacetate esterase
C3
complement component 3
if
immunofluorescence
HPV16
human papillomavirus 16

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