Premium
Alterations in hepatic tumor cell colonization during obesity
Author(s) -
O'Leary Heather A.,
Kothur Anand,
Goodwill Adam G.,
Frisbee Jefferson C.,
Brock Robert W.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.639.2
Subject(s) - colonization , obesity , cell , cancer research , biology , medicine , microbiology and biotechnology , genetics
Epidemiological studies have demonstrated the tumor metastatic‐promoting effects of obesity, including increased colonization, linked to its chronic inflammatory state. Yet, the initiating steps of tumor colonization at metastatic sites, specifically the liver, have not been fully elucidated. Therefore we chose to examine how obesity alters the initiating steps of hepatic tumor colonization in genetically hyperphagic mice (ob/ob & db/db) with a C57BL/6 background. Syngeneic B16 melanoma cells were fluorescently labeled with a green PKH dye and hydrodynamically injected into obese and lean mice to isolate hepatic colonization. Mice livers were subsequently imaged by intravital microscopy at day 0, 3 and 5 days so the number of tumor foci, tumor size, as well as alterations to basal sinusoidal microvascular function were investigated. Despite lean mice initially retaining higher numbers of single tumor foci than the obese mice, the obese mice possessed significantly larger masses of cells. These initial differences were magnified over time. Both of these spatial and temporal differences occurred with concomitant alterations to basal sinusoidal perfusion. Together, these data suggest that obesity predisposes the liver to enhanced tumor colonization via increased growth of tumor cell foci.