| First Author | Kojima Y | Year | 2019 |
| Journal | Cancer Sci | Volume | 110 |
| Issue | 8 | Pages | 2520-2528 |
| PubMed ID | 31215118 | Mgi Jnum | J:288968 |
| Mgi Id | MGI:6434911 | Doi | 10.1111/cas.14100 |
| Citation | Kojima Y, et al. (2019) Stromal iodothyronine deiodinase 2 (DIO2) promotes the growth of intestinal tumors in Apc(Delta716) mutant mice. Cancer Sci 110(8):2520-2528 |
| abstractText | Iodothyronine deiodinase 2 (DIO2) converts the prohormone thyroxine (T4) to bioactive T3 in peripheral tissues and thereby regulates local thyroid hormone (TH) levels. Although epidemiologic studies suggest the contribution of TH to the progression of colorectal cancer (CRC), the role of DIO2 in CRC remains elusive. Here we show that Dio2 is highly expressed in intestinal polyps of Apc(Delta716) mice, a mouse model of familial adenomatous polyposis and early stage sporadic CRC. Laser capture microdissection and in situ hybridization analysis show almost exclusive expression of Dio2 in the stroma of Apc(Delta716) polyps in the proximity of the COX-2-positive areas. Treatment with iopanoic acid, a deiodinase inhibitor, or chemical thyroidectomy suppresses tumor formation in Apc(Delta716) mice, accompanied by reduced tumor cell proliferation and angiogenesis. Dio2 expression in Apc(Delta716) polyps is strongly suppressed by treatment with the COX-2 inhibitor meloxicam. Analysis of The Cancer Genome Atlas data shows upregulation of DIO2 in CRC clinical samples and a close association of its expression pattern with the stromal component, consistently with almost exclusive expression of DIO2 in the stroma of human CRC as revealed by in situ hybridization. These results indicate essential roles of stromal DIO2 and thyroid hormone signaling in promoting the growth of intestinal tumors. |
