| Abstract |
Breast cancer is the first cause of death from female cancer. The
recurrence of the disease originated at the level of secondary organs, or
metastasis, is responsible for 90% of deaths from cancer. The factors that
endow these cells with metastatic functions are largely unknown. One of
the limitations in the study of tumor cells with metastatic phenotypes is
that cell lines maintained in culture lose this ability to invade and
colonize tissues. On the other hand, it has been shown that reinjection of
cells in animals can lead to their enrichment with aggressive phenotypes.
The aim of this work was the isolation and characterization of different
cell populations with differentiated metastatic capacities. Following
inoculation of the F3II murine mammary carcinoma cell lines, we
established cell populations in vitro, one from the primary tumor and
another from a metastatic nodule, F3II TP and F3II NM cell lines
respectively. To determine their aggressiveness, a series of additional
characteristics were compared between these lines and F3II. The three
lines showed variations in morphology in culture and a different doubling
time, with F3II NM having the highest one. Moreover, F3II NM presented
major adhesion capacity and lower clonogenic potential. This could be
explained by the differential expression of cell adhesion molecules, such
as integrins or cadherins analyzed by flow cytometry. In addition, the
migration capacity was analyzed by transwell assay and the results showed
differences in this process. Finally, we compared the behavior in vivo and
we detected variations in tumor progression such as latency, frequency of
ulceration, tumor growth and the presence of pulmonary nodules. All things
considered, the establishment and characterization of these two new
different cell lines with differentiated metastatic capacities will allow
us to determine molecular differences involved in the metastatic process.
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