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Hypothyroidism enhances tumor invasiveness and metastasis development.

Martínez-Iglesias O, García-Silva S, Regadera J, Aranda A - PLoS ONE (2009)

Bottom Line: In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRbeta-expressing cells were injected into euthyroid nude mice.Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs.On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid, Madrid, Spain.

ABSTRACT

Background: Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients

Methodology/principal findings: In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRbeta1-expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRbeta-expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs.

Conclusions/significance: These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.

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Hypothyroidism reduces Cyclin E expression and BrdU incorporation.(A)-Immunohistochemical staining for Cyclin E in biopsies from SK, SK-TRβ, MDA and MDA-TRβ tumors developed in control and hypothyroid nude mice. (B)-Quantification of the percentage of cells expressing Cyclin E in tumors of the different groups. (C)-BrdU incorporation was measured in explants from SK and SK-TRβ tumors resected after 25 days of inoculation in control and hypothyroid mice.
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pone-0006428-g004: Hypothyroidism reduces Cyclin E expression and BrdU incorporation.(A)-Immunohistochemical staining for Cyclin E in biopsies from SK, SK-TRβ, MDA and MDA-TRβ tumors developed in control and hypothyroid nude mice. (B)-Quantification of the percentage of cells expressing Cyclin E in tumors of the different groups. (C)-BrdU incorporation was measured in explants from SK and SK-TRβ tumors resected after 25 days of inoculation in control and hypothyroid mice.

Mentions: Expression of Cyclin E, other proliferation marker, was reduced in biopsies of both hepatocarcinoma (Figure 4A) and breast cancer tumors (Figure 4B) developed in hypothyroid hosts, and also in this case the effect was observed independently of the presence of TRβ. In addition, reduced proliferation, assessed by BrdU incorporation, was observed in explants obtained from SK and SK-TRβ tumors when xenografts were grown in hypothyroid hosts (Figure 4C).


Hypothyroidism enhances tumor invasiveness and metastasis development.

Martínez-Iglesias O, García-Silva S, Regadera J, Aranda A - PLoS ONE (2009)

Hypothyroidism reduces Cyclin E expression and BrdU incorporation.(A)-Immunohistochemical staining for Cyclin E in biopsies from SK, SK-TRβ, MDA and MDA-TRβ tumors developed in control and hypothyroid nude mice. (B)-Quantification of the percentage of cells expressing Cyclin E in tumors of the different groups. (C)-BrdU incorporation was measured in explants from SK and SK-TRβ tumors resected after 25 days of inoculation in control and hypothyroid mice.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2712768&req=5

pone-0006428-g004: Hypothyroidism reduces Cyclin E expression and BrdU incorporation.(A)-Immunohistochemical staining for Cyclin E in biopsies from SK, SK-TRβ, MDA and MDA-TRβ tumors developed in control and hypothyroid nude mice. (B)-Quantification of the percentage of cells expressing Cyclin E in tumors of the different groups. (C)-BrdU incorporation was measured in explants from SK and SK-TRβ tumors resected after 25 days of inoculation in control and hypothyroid mice.
Mentions: Expression of Cyclin E, other proliferation marker, was reduced in biopsies of both hepatocarcinoma (Figure 4A) and breast cancer tumors (Figure 4B) developed in hypothyroid hosts, and also in this case the effect was observed independently of the presence of TRβ. In addition, reduced proliferation, assessed by BrdU incorporation, was observed in explants obtained from SK and SK-TRβ tumors when xenografts were grown in hypothyroid hosts (Figure 4C).

Bottom Line: In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRbeta-expressing cells were injected into euthyroid nude mice.Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs.On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Investigaciones Biomédicas, Consejo Superior de Investigaciones Científicas y Universidad Autónoma de Madrid, Madrid, Spain.

ABSTRACT

Background: Whereas there is increasing evidence that loss of expression and/or function of the thyroid hormone receptors (TRs) could result in a selective advantage for tumor development, the relationship between thyroid hormone levels and human cancer is a controversial issue. It has been reported that hypothyroidism might be a possible risk factor for liver and breast cancer in humans, but a lower incidence of breast carcinoma has been also reported in hypothyroid patients

Methodology/principal findings: In this work we have analyzed the influence of hypothyroidism on tumor progression and metastasis development using xenografts of parental and TRbeta1-expressing human hepatocarcinoma (SK-hep1) and breast cancer cells (MDA-MB-468). In agreement with our previous observations tumor invasiveness and metastasis formation was strongly repressed when TRbeta-expressing cells were injected into euthyroid nude mice. Whereas tumor growth was retarded when cells were inoculated into hypothyroid hosts, tumors had a more mesenchymal phenotype, were more invasive and metastatic growth was enhanced. Increased aggressiveness and tumor growth retardation was also observed with parental cells that do not express TRs.

Conclusions/significance: These results show that changes in the stromal cells secondary to host hypothyroidism can modulate tumor progression and metastatic growth independently of the presence of TRs on the tumor cells. On the other hand, the finding that hypothyroidism can affect differentially tumor growth and invasiveness can contribute to the explanation of the confounding reports on the influence of thyroidal status in human cancer.

Show MeSH
Related in: MedlinePlus