A research group led by Professor Ryohei Nishimura of the University of Tokyo and Professor Yukinari Kato of Tohoku University has revealed that there is a common metastasis-promoting mechanism in mucosal-derived malignant melanoma in humans and dogs.
Malignant melanoma derived from the mucous membrane in humans has a low incidence of about 1-2% of all malignant melanomas, and is classified as a "rare cancer."In addition, it has a higher metastasis rate than cutaneous malignant melanoma, which accounts for about 90% of malignant melanoma, and its 5-year survival rate is about 20%, which is extremely poor prognosis.
On the other hand, mucosal-type malignant melanoma in dogs is known to have a relatively high incidence, especially canine oral malignant melanoma originating from the oral mucosa accounts for about 70% of all malignant melanomas.The characteristics of high metastasis rate and poor prognosis are similar to human malignant melanoma.
Our research group has previously found that a membrane protein called podoplanin (PDPN) is highly expressed in dogs with oral malignant melanoma. Overexpression of PDPN has been reported in various malignant tumors, and as a result of more detailed investigation of PDPN expression in patients with mucosal malignant melanoma, metastasis occurred earlier in patients with high PDPN expression in both humans and dogs. found to have a short prognosis.
Therefore, we verified that PDPN promotes metastasis, and found that PDPN activates the downstream Rho-associated kinase-Myosin light chain 2 (ROCK-MLC2) signal, resulting in an amoeboid metastasis in PDPN-highly expressed tumor cells. We found that migration was induced.Amoeba-like migratory cells can pass through the gaps between normal cells by freely changing their shape like amoebae.More interestingly, the pattern of gene variation associated with amoeba-like migration was very similar in human and canine malignant melanoma, suggesting that PDPN regulates a common metastatic mechanism in human and canine malignant melanoma. It is considered possible that
The results of this study have revealed that PDPN is a promising new therapeutic target for mucosal-derived malignant melanoma in humans and dogs, and that canine malignant melanoma has important value in human cancer research. It can also be said that
Paper information:[Molecular Cancer Research] Podoplanin drives amoeboid invasion in canine and human mucosal melanoma
