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Tumor Colonization (tumor + colonization)

Distribution by Scientific Domains

Medical Sciences	100%

Selected Abstracts

Epidermal growth factor receptor and claudin-2 participate in A549 permeability and remodeling: Implications for non-small cell lung cancer tumor colonization

MOLECULAR CARCINOGENESIS, Issue 6 2009
Yakov Peter
Abstract Tumor colonization involves changes in cell permeability and remodeling. Paracellular permeability is regulated by claudins, integrated tight junction (TJ) proteins, located on the apicolateral portion of epithelial cells. Epidermal growth factor (EGF) was reported to modify cellular claudin levels and induce remodeling. To investigate a role for EGF receptor (EGFR) activation in tumor colonization we studied the effect of EGF and claudin-2 overexpression on permeability and cell reorganization in the human A549 non-small cell lung cancer (NSCLC) cell line. Our data demonstrated that A549 cells possess functional TJs and that EGF treatment increased levels of claudin-2 expression by 46%. Furthermore, EGFR signaling reduced monolayer permeability to choline and triggered cellular remodeling. The mitogen-activated protein kinase inhibitor PD98059 blocked the effect on A549 permeability and remodeling. EGF stimulation also exacerbated a fourfold increase in cell colonization elicited by claudin-2 upregulation. Our findings are consistent with the hypothesis that EGFR signaling plays an important role in A549 cell physiology and acts synergistically with claudin-2 to accelerate tumor colonization. Understanding the influence of EGF on A549 cell permeability and reorganization will help shed light on NSCLC tumor colonization and contribute to the development of novel anti-cancer treatments. © 2008 Wiley-Liss, Inc. [source]

Imaging the effects of castration on bone turnover and hormone-independent prostate cancer colonization of bone

THE PROSTATE, Issue 15 2008
N.A. Cross
Abstract INTRODUCTION Tumor populations may selectively colonize bone that is being actively remodeled. In prostate cancer patients, androgen deprivation directly inhibits tumor growth initially, whilst induced bone loss may facilitate tumor colonization of bone by androgen-insensitive cells. We have tested this hypothesis using a xenograft model of early growth of prostate cancer in bone. METHODS PC3 cells transfected with Green fluorescent protein (GFP) were injected into castrated and non-castrated athymic mice via intrabial and intracardiac routes. In vivo tumor growth was monitored daily and animals sacrificed 6,9 days following initial GFP-based detection of tumors. Tumor bearing and contra-lateral non-tumor bearing tibias were analyzed extensively by micro-CT and histology/immunohistochemistry for the presence of tumor cells and the effects of tumor and/or castration on bone cells and bone structure evaluated. RESULTS GFP-positive tumors in bone were visible from 12 days post-injection following intratibial injection, allowing tumors <1 mm diameter to be monitored in live animals. Castration did not affect tumor frequency, tumor volume, or time to initial appearance of tumors injected via intratibial or intracardiac routes. Castration decreased trabecular bone volume in all mice. Significant tumor-induced suppression of numbers of osteoblasts, coupled with increased numbers of activated osteoclasts, was evident in both intact animals and castrated animals. CONCLUSIONS In vivo GFP imaging allows the detection of early tumor growth at intra-osseous sites. Castration induces bone loss, but PC3-GFP cells are also capable of inducing bone remodeling in intact animals at early time points, independently of pre-existing castration-induced alterations to bone. Prostate 68: 1707,1714, 2008. © 2008 Wiley-Liss, Inc. [source]