h-prune affects anaplastic thyroid cancer invasion and metastasis.
Anaplastic thyroid cancer is one of the most aggressive human malignancies and is resistant to multimodal treatments. The expression of h-prune, the human homologue of Drosophila prune, has been reported to be correlated with progression and aggressiveness in various cancers including breast, colorectal and pancreatic cancers. We examined the role of h-prune in anaplastic thyroid cancer cell migration, invasion and metastasis. Immunohistochemical analysis of h-prune was performed with 15 surgically resected specimens of anaplastic thyroid cancers. To investigate cell motility, Boyden chamber, wound healing and matrigel invasion assays were performed using cells from anaplastic thyroid cancer cell lines. A murine orthotopic thyroid cancer model was used to investigate metastatic ability. In the immunohistochemical analysis, only weak focal or no staining of h-prune was observed in non-tumor tissue. In contrast, diffuse staining of h-prune was observed in anaplastic thyroid cancer and lymph node metastasis samples. Both inhibition of h-prune phosphodiesterase activity with dipyridamole and small interfering RNA for h-prune suppressed 8505C and KTC-3 cell motility. In addition, treatment with dipyridamole and decreased expression of h-prune suppressed tumor invasion and pulmonary metastasis in a NOD/Shi-scid, IL-2Rγnull (NOG) mouse orthotopic thyroid cancer model. In conclusion, h-prune is frequently expressed in anaplastic thyroid cancer cells and lymph nodes metastasis, and promotes migration and invasion of anaplastic thyroid cancer cells and metastasis in an anaplastic thyroid cancer model. Thus, h-prune shows promise as a targeting candidate against anaplastic thyroid cancer.
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Junko
J
Nambu
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Tsuyoshi
T
Kobayashi
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Masakazu
M
Hashimoto
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hirotaka
H
Tashiro
Department of Surgery, Tsuchiya General Hospital, Hiroshima, Japan.
Keizo
K
Sugino
Department of Health Science, Faculty of Human Culture and Society, Prefectural University of Hiroshima, Faculty of Human Culture and Society, Hiroshima, Japan.
Fumio
F
Shimamoto
Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Osaka, Japan.
Akira
A
Kikuchi
Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hideki
H
Ohdan
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D009361:Neoplasm Invasiveness; D010744:Phosphoric Monoester Hydrolases; D065646:Thyroid Carcinoma, Anaplastic / Q000473:pathology*
D002352:Carrier Proteins; C438732:PRUNE1 protein, human; D010744:Phosphoric Monoester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases