INVESTIGADORES
LAMB Caroline Ana
artículos
Título:
Inoculated mammary carcinoma-associated fibroblasts: contribution to hormone independent tumor growth
Autor/es:
FABRIS, VICTORIA; SAHORES, ANA; VANZULLI, SILVIA; COLOMBO, LUCAS; MOLINOLO, ALFREDO; LANARI, CLAUDIA; LAMB, CAROLINE A.
Revista:
BMC CANCER
Editorial:
BIOMED CENTRAL LTD
Referencias:
Año: 2010 vol. 10 p. 293 - 303
ISSN:
1471-2407
Resumen:
Abstract
Background: Increasing evidence has underscored the role of carcinoma associated fibroblasts (CAF) in tumor growth.
However, there are controversial data regarding the persistence of inoculated CAF within the tumors. We have
developed a model in which murine metastatic ductal mammary carcinomas expressing estrogen and progesterone
receptors transit through different stages of hormone dependency. Hormone dependent (HD) tumors grow only in the
presence of progestins, whereas hormone independent (HI) variants grow without hormone supply. We demonstrated
previously that CAF from HI tumors (CAF-HI) express high levels of FGF-2 and that FGF-2 induced HD tumor growth in
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
However, there are controversial data regarding the persistence of inoculated CAF within the tumors. We have
developed a model in which murine metastatic ductal mammary carcinomas expressing estrogen and progesterone
receptors transit through different stages of hormone dependency. Hormone dependent (HD) tumors grow only in the
presence of progestins, whereas hormone independent (HI) variants grow without hormone supply. We demonstrated
previously that CAF from HI tumors (CAF-HI) express high levels of FGF-2 and that FGF-2 induced HD tumor growth in
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
Increasing evidence has underscored the role of carcinoma associated fibroblasts (CAF) in tumor growth.
However, there are controversial data regarding the persistence of inoculated CAF within the tumors. We have
developed a model in which murine metastatic ductal mammary carcinomas expressing estrogen and progesterone
receptors transit through different stages of hormone dependency. Hormone dependent (HD) tumors grow only in the
presence of progestins, whereas hormone independent (HI) variants grow without hormone supply. We demonstrated
previously that CAF from HI tumors (CAF-HI) express high levels of FGF-2 and that FGF-2 induced HD tumor growth in
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
in
vivo. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
induce HD tumor growth.
. Our main goal was to investigate whether inoculated CAF-HI combined with purified epithelial (EPI) HD cells can
induce HD tumor growth.
Methods: Purified EPI cells of HD and HI tumors were inoculated alone, or together with CAF-HI, into female BALB/c
mice and tumor growth was evaluated. In another set of experiments, purified EPI-HI alone or combined with CAF-HI
or CAF-HI-GFP were inoculated into BALB/c or BALB/c-GFP mice. We assessed whether inoculated CAF-HI persisted
within the tumors by analyzing inoculated or host CAF in frozen sections of tumors growing in BALB/c or BALB/c-GFP
mice. The same model was used to evaluate early stages of tumor development and animals were euthanized at 2, 7,
12 and 17 days after EPI-HI or EPI-HI+CAF-HI inoculation. In angiogenesis studies, tumor vessels were quantified 5 days
after intradermal inoculation.
mice and tumor growth was evaluated. In another set of experiments, purified EPI-HI alone or combined with CAF-HI
or CAF-HI-GFP were inoculated into BALB/c or BALB/c-GFP mice. We assessed whether inoculated CAF-HI persisted
within the tumors by analyzing inoculated or host CAF in frozen sections of tumors growing in BALB/c or BALB/c-GFP
mice. The same model was used to evaluate early stages of tumor development and animals were euthanized at 2, 7,
12 and 17 days after EPI-HI or EPI-HI+CAF-HI inoculation. In angiogenesis studies, tumor vessels were quantified 5 days
after intradermal inoculation.
Purified EPI cells of HD and HI tumors were inoculated alone, or together with CAF-HI, into female BALB/c
mice and tumor growth was evaluated. In another set of experiments, purified EPI-HI alone or combined with CAF-HI
or CAF-HI-GFP were inoculated into BALB/c or BALB/c-GFP mice. We assessed whether inoculated CAF-HI persisted
within the tumors by analyzing inoculated or host CAF in frozen sections of tumors growing in BALB/c or BALB/c-GFP
mice. The same model was used to evaluate early stages of tumor development and animals were euthanized at 2, 7,
12 and 17 days after EPI-HI or EPI-HI+CAF-HI inoculation. In angiogenesis studies, tumor vessels were quantified 5 days
after intradermal inoculation.
Results: We found that admixed CAF-HI failed to induce epithelial HD tumor growth, but instead, enhanced HI tumor
growth (p < 0.001). Moreover, inoculated CAF-HI did not persist within the tumors. Immunofluorescence studies
showed that inoculated CAF-HI disappeared after 13 days. We studied the mechanisms by which CAF-HI increased HI
tumor growth, and found a significant increase in angiogenesis (p < 0.05) in the co-injected mice at early time points.
growth (p < 0.001). Moreover, inoculated CAF-HI did not persist within the tumors. Immunofluorescence studies
showed that inoculated CAF-HI disappeared after 13 days. We studied the mechanisms by which CAF-HI increased HI
tumor growth, and found a significant increase in angiogenesis (p < 0.05) in the co-injected mice at early time points.
We found that admixed CAF-HI failed to induce epithelial HD tumor growth, but instead, enhanced HI tumor
growth (p < 0.001). Moreover, inoculated CAF-HI did not persist within the tumors. Immunofluorescence studies
showed that inoculated CAF-HI disappeared after 13 days. We studied the mechanisms by which CAF-HI increased HI
tumor growth, and found a significant increase in angiogenesis (p < 0.05) in the co-injected mice at early time points.
Conclusions: Inoculated CAF-HI do not persist within the tumor mass although they play a role during the first stages
of tumor formation promoting angiogenesis. This angiogenic environment is unable to replace the hormone
requirement of HD tumors that still need the hormone to recruit the stroma from the host.
of tumor formation promoting angiogenesis. This angiogenic environment is unable to replace the hormone
requirement of HD tumors that still need the hormone to recruit the stroma from the host.
Inoculated CAF-HI do not persist within the tumor mass although they play a role during the first stages
of tumor formation promoting angiogenesis. This angiogenic environment is unable to replace the hormone
requirement of HD tumors that still need the hormone to recruit the stroma from the host.