Sex Hormones May Play Role in Follicular Thyroid Cancer

Sex hormones may significantly affect the development and progression of follicular thyroid cancer, according to data presented at the 84th Annual Meeting of the American Thyroid Association, with researchers also identifying how male sex hormones influence cancer progression.

It is well documented that thyroid cancer is much more prevalent in women. However, it is more common for men to be diagnosed with more aggressive disease.

To better understand this gender difference, Lisa Zhang, PhD, of the National Cancer Institute in Bethesda, Maryland, and colleagues evaluated the effects of sex hormones on thyroid cancer using a mouse model that mimics human follicular thyroid cancer (FTC) development.

The researchers performed sham surgery or castration on 6-week-old mice and then examined their hormone status and thyroid cancer when the mice were 8 to 9 months old.

They found that castration led to lower rates of thyroid cancer in female mice and less advanced cancer in male mice, suggesting that sex hormones may play an important role in the development and progression of FTC. Further, in castrated male mice, testosterone replacement therapy reversed the slow progression.

The researchers also found that testosterone regulates the expression of tumor-suppressor genes and affects tumor immunity.

“We think our findings demonstrate that sex hormones have a significant role on the rate of thyroid cancer in females and how aggressive it is in males,” said Dr. Zhang.

When the researchers examined the mechanisms of action they found the less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immunoregulatory genes.  They also found there was a higher tumor infiltration with M1 macrophages and CD8 positive cells.

The study demonstrated that exogenous testosterone helped reverse the differences in FTC progression and the molecular and cellular changes observed with castration.

The researchers also examined human FTC samples and found reduced expression of GLIPR1 and SFRP1 compared with normal thyroid tissue. The findings suggested that knockdown of GLIPR1 in human cells increased cellular proliferation and colony formation. This helped to decease CCL5 secretion, a chemokine known to have a role in attraction and activation of immune cells.

“There is a biological basis for the gender disparity we see clinically in thyroid cancer patients,” Dr. Zhang told Endocrinology Advisor. “We are performing follow-up studies to determine the critical factors for the different rate of thyroid cancer we saw in our initial analysis.”

Reference

1. Zhang LJ et al. Oral Abstract 6. Presented at: American Thyroid Association (ATA) 84th Annual Meeting; Oct. 29-Nov. 2, 2014; Coronado, Calif.