LETTERS TO THE EDITOR Ror2 may be downregulated in oral squamous cell carcinoma

To the Editor: The article by Masaki K. et al. suggested that Ror2 expression in oral cancer was significantly higher than that in the normal oral mucosa. In their experiments, the normal tissue segments were from healthy volunteers. And in the Western blot figure, the 3 cases were not shown which region the tumor specimens were from. The normal tissue and the tumor specimens were from different person and different region of mouth. They did not even show whether the Ror2 expression in the gingiva, cheeks mucosa, tongue, and floor of the mouth was identical or not. Therefore, their normal tissue segments and tumor specimens may be not comparable. According to our recent study, Ror2 was downregulated in oral squamous cell carcinoma (OSCC). We investigated protein level of Ror2 in 11 patients with moderately and poorly differentiated tongue OSCC. We used the adjacent epithelial of the tumor specimen from the same patient as the normal tissue. Therefore, our results are much more convincing. Previous studies have shown that Ror2 was downregulated and served as a tumor suppressor in colon cancer and hepatocellular carcinoma. And Ror2 also is a co-receptor of Wnt5a, they can form a complex to activate Wnt/planar cell polarity (PCP) signaling and inhibit Wnt/b signaling. Wnt/PCP signaling plays a complex role in cancer development. At early stages of cancer, Wnt/PCP signaling inhibits cancer progression by antagonizing Wnt/b signaling. As tumor progress, Wnt/PCP signaling gets activated and promotes tumor cell migration and invasion and supports angiogenesis, contributing to metastasis in late stages of cancer. It has been already identified that Wnt/b signaling is activated in oral cancer. Therefore, Ror2 may be serve as a tumor suppressor at the early stages of OSCC, but a promoter at the late stages. Thus our result of the downregulation of Ror2 in OSCC, at least in the early stages of oral cancer, will make sense. However, we did not get the upregulation of Ror2 in any case that we used in our experiment. Therefore, further studies should be performed to confirm whether the expression of Ror2 is upregulated at final stage of oral cancer to activate the Wnt/PCP signaling and promote the tumor spread, and whether the Ror2 expression in the gingiva, cheeks mucosa, tongue and floor of the mouth is identical.