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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 tumor proliferation and increases necrosis.(A)-The percentage of cells expressing the proliferation marker Ki67 was determined by immunohistochemistry in biopsies of the tumors formed by parental and TRβ-expressing SK and MDA cells in control and hypothyroid nude mice. (B)-Hypothyroidism increased the necrotic area of the tumors determined from H& staining. Data are mean±S.E.
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pone-0006428-g003: Hypothyroidism reduces tumor proliferation and increases necrosis.(A)-The percentage of cells expressing the proliferation marker Ki67 was determined by immunohistochemistry in biopsies of the tumors formed by parental and TRβ-expressing SK and MDA cells in control and hypothyroid nude mice. (B)-Hypothyroidism increased the necrotic area of the tumors determined from H& staining. Data are mean±S.E.

Mentions: The reduced tumor volume in hypothyroid hosts correlated with a lower proliferation in tumor biopsies obtained at the end of the experimental period (Figure 3A). Ki67 labeling showed that tumors originated in control mice from parental SK and MDA cells were highly proliferative and that hypothyroidism reduced the number of cells expressing this proliferation marker. In addition, TRβ-expressing cells gave rise to tumors with a lower proliferation index and this reduction was stronger in MDA-TRβ tumors in the hypothyroid mice. Decreased proliferation was accompanied by enlargement of the necrotic area of the tumors grown in hypothyroid mice and, as shown in Figure 3B, this increase occurred both in parental and TRβ-expressing cells.


Hypothyroidism enhances tumor invasiveness and metastasis development.

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

Hypothyroidism reduces tumor proliferation and increases necrosis.(A)-The percentage of cells expressing the proliferation marker Ki67 was determined by immunohistochemistry in biopsies of the tumors formed by parental and TRβ-expressing SK and MDA cells in control and hypothyroid nude mice. (B)-Hypothyroidism increased the necrotic area of the tumors determined from H& staining. Data are mean±S.E.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0006428-g003: Hypothyroidism reduces tumor proliferation and increases necrosis.(A)-The percentage of cells expressing the proliferation marker Ki67 was determined by immunohistochemistry in biopsies of the tumors formed by parental and TRβ-expressing SK and MDA cells in control and hypothyroid nude mice. (B)-Hypothyroidism increased the necrotic area of the tumors determined from H& staining. Data are mean±S.E.
Mentions: The reduced tumor volume in hypothyroid hosts correlated with a lower proliferation in tumor biopsies obtained at the end of the experimental period (Figure 3A). Ki67 labeling showed that tumors originated in control mice from parental SK and MDA cells were highly proliferative and that hypothyroidism reduced the number of cells expressing this proliferation marker. In addition, TRβ-expressing cells gave rise to tumors with a lower proliferation index and this reduction was stronger in MDA-TRβ tumors in the hypothyroid mice. Decreased proliferation was accompanied by enlargement of the necrotic area of the tumors grown in hypothyroid mice and, as shown in Figure 3B, this increase occurred both in parental and TRβ-expressing cells.

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