Higher Integrin Alpha 3 Beta1 Expression in Papillary Thyroid Cancer Is Associated with Worst Outcome (original) (raw)
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Integrins in thyroid tissue: upregulation of alpha2beta1 in anaplastic thyroid carcinoma
European Journal of Endocrinology, 1998
OBJECTIVE: To evaluate the integrin pattern in the normal thyroid gland and in different pathological disorders including malignant tumors, because the aggressiveness of several malignant tumors correlates with alterations in the expression of one or more integrins. DESIGN: We examined the expression of integrins and E-cadherin immunohistochemically in a large and well-defined sample of normal and pathological human thyroid tissue. METHODS: Cryosections of 58 thyroid tissue specimens from normal tissue, thyrotoxicosis, nodular goiter, oxyphilic adenoma, follicular adenoma, follicular carcinoma, papillary carcinoma and anaplastic carcinoma, and three lymph node metastases were investigated immunohistochemically using monoclonal antibodies specifically recognizing the integrin beta1-, beta4-, alpha1-, alpha2-, alpha3-, alpha5- and alpha6-subunits, or E-cadherin. RESULTS: All thyroid epithelial cells expressed integrin beta1- and alpha3-subunits. Immunostaining of the beta4-subunit and...
Molecular Imaging and Radionuclide Therapy, 2022
Objectives: The important roles of integrins in tumor invasion, migration and proliferation are well known. In this study, we investigated the presence of integrin α3 and β1 receptors in tumor tissue, metastatic lymph node (LN) and normal thyroid tissue of patients diagnosed with thyroid cancer (TCa) and showed the prognostic and diagnostic value of these molecules as well as peptide-receptor. Methods: Sixty-one patients with TCa were included in this study. The presence of integrin α3 and β1 expression was investigated by immunohistochemical methods from tumor tissue after total thyroidectomy. TNM system was used in tumor staging. The relationship between prognostic properties such as tumor size, LN metastasis, capsular invasion and the presence of integrin α3 and β1 expression was investigated. Results: Classical type papillary TCa was the most common subtype in our study group with 31.1%. Integrin β1 was expressed in 4.9% (n=3) of normal tissue, 57.4% (n=35) of tumor tissue and 16.4% (n=10) of metastatic LN; integrin α3 was expressed in 50.8% (n=31) of normal tissue, 67.2% (n=41) of tumor tissue and 9.8% (n=6) metastatic LN. Integrin β1 expression was observed 21.3% (n=13), integrin α3 in 14.8% (n=9) and integrin α3 and β1 expression in 36.1% (n=22). Integrin β1 expression increased statistically significantly in the presence of LN metastasis and capsular invasion (p=0.022, 0.014, respectively). Furthermore, the expression of integrin α3 was found to be statistically significant in primary tumors of patients with LN metastasis (p=0.045). Conclusion: Our study showed a significant increase in integrin α3 and β1 expression in LN metastasis or thyroid capsule invasion in tumor. Thus, it appears that the demonstration of the presence of integrin α3 and β1 expression in TCa is not only a prognostic biomarker but also has value as a potential theranostic target with peptide-bound radioactive agents.
Loss of polarity andDe novo expression of the β1 family of integrins in thyroid tumors
International Journal of Cancer, 1994
The expression and cell-membrane distribution of the PI family of integrins (very-late-activation antigens, VLA) were investigated in benign and malignant human thyroid tumors. We compared tissue samples of normal glands, nodular goiters, adenomas and carcinomas. We also examined 3 thyroidcarcinoma cell lines cultured in vitro. The expression of subunits of the PI family of integrins was assessed by flow cytometry and specific antibodies in dispersed single-cell suspensions and by immunofluorescence on frozen tissue sections. In contrast to the heterogeneity of the expression of PI integrins observed in other tumors, thyroid neoplastic lesions showed a remarkably constant VLA profile. In all tumors, benign as well as malignant, and in carcinoma cell lines, all sub-units of PI integrins were expressed at high levels. While sub-units a,, a,, %, % and occasionally a2 were also present in a cell sub-set of normal glands and nodular goiters, expression of a, was restricted to neoplastic lesions; this integrin can be therefore considered an antigen associated with thyroid tumors. It has been reported that in normal glands and in nodular goiters, the expression of Received: June 30,1994.
Activation of integrin-ERBB2 signaling in undifferentiated thyroid cancer
American journal of cancer research, 2014
Undifferentiated thyroid carcinoma is one of the most aggressive human cancers. Although genetic changes underlying this aggressive cancer remain to be elucidated, RAS mutations have been frequently identified in it. Mice harboring a mutant thyroid hormone receptor Thrb(PV) (Thrb(PV/PV) ) spontaneously develop differentiated follicular thyroid carcinoma similar to human thyroid cancer. We recently demonstrated that targeting a RAS mutation (Kras(G12D) ) to the thyroid of Thrb(PV/PV) mice (Thrb(PV/PV) Kras(G12D) mice) promotes initiation and progression of undifferentiated thyroid cancer. To uncover genes destined to drive the aggressive cancer phenotype, we used cDNA microarrays to compare the gene expression profiles of thyroid cells of Kras(G12D) mice and thyroid tumor lesions of Thrb(PV/PV) and Thrb(PV/PV) Kras(G12D) mice. Analyses of microarray data identified 14 upstream regulators that were significantly altered in thyroid tumors of Thrb(PV/PV) and Thrb(PV/PV) Kras(G12D) mice....
PloS one, 2011
A cell surface receptor for thyroid hormone that activates extracellular regulated kinase (ERK) 1/2 has been identified on integrin αvβ3. We have examined the actions of thyroid hormone initiated at the integrin on human NCI-H522 non-small cell lung carcinoma and NCI-H510A small cell lung cancer cells. At a physiologic total hormone concentration (10(-7) M), T(4) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T(3)) at a supraphysiologic concentration. Neutralizing antibody to integrin αvβ3 and an integrin-binding Arg-Gly-Asp (RGD) peptide blocked thyroid hormone-induced PCNA expression. Tetraiodothyroacetic acid (tetrac) lacks thyroid hormone function but inhibits binding of T(4) and T(3) to the integrin receptor; tetrac eliminated thyroid hormone-induced lung cancer cell proliferation and ERK1/2 activation. In these estrogen receptor-α (ERα)-positive lung cancer cells, thyroid hormone (T(4)&g...
Oncotarget, 2016
Ovarian cancer is the leading cause of death in gynecological diseases. Thyroid hormone promotes proliferation of ovarian cancer cells via cell surface receptor integrin αvβ3 that activates extracellular regulated kinase (ERK1/2). However, the mechanisms are still not fully understood. Thyroxine (T4) at a physiologic total hormone concentration (10-7 M) significantly increased proliferating cell nuclear antigen (PCNA) abundance in these cell lines, as did 3, 5, 3'-triiodo-L-thyronine (T3) at a supraphysiologic concentration. Thyroid hormone (T4 and T3) treatment of human ovarian cancer cells resulted in enhanced activation of the Ras/MAPK(ERK1/2) signal transduction pathway. An MEK inhibitor (PD98059) blocked hormone-induced cell proliferation but not ER phosphorylation. Knock-down of either integrin αv or β3 by RNAi blocked thyroid hormone-induced phosphorylation of ERK1/2. We also found that thyroid hormone causes elevated phosphorylation and nuclear enrichment of estrogen rec...
World Journal of Surgery, 1992
FTC-238 cell extract and conditioned media exhibited a more complex array of proteases consistent with activated type 1 collagenase and stromelysin compared to the less invasive clones, however 72 and 92 kd gelatinases consistent with type IV collagenases were present in the conditioned media from all three lines. In conclusion, in vitro invasion parallels in vivo metastasis by the source cells in the FTC-133/236/238 cell-lines. The ability to invade basement membrane preparation correlates with increased synthesis and expression of/31 integrins and activation of tumor proteases.
Thyroid Hormone Controls Breast Cancer Cell Movement via Integrin αV/β3/SRC/FAK/PI3-Kinases
Hormones & cancer, 2017
Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/β3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cell...