Format

Send to

Choose Destination
Neoplasia. 2004 Nov-Dec;6(6):768-76.

Early neoplastic progression is complement independent.

Author information

1
Cancer Research Institute, University of California, San Francisco, 2340 Sutter Street, San Francisco, CA 94143, USA.

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 complement-independent pathways are critical for leukocyte recruitment into neoplastic tissue and leukocyte-mediated potentiation of tumorigenesis.

PMID:
15720803
PMCID:
PMC1531681
DOI:
10.1593/neo.04250
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center