Occult metastasis of cancer cells in an orthotopically implanted oral cancer model - Reproduce the occult metastasis

To reproduce the initial stage of metastatic focus formation by cancer cells, we serially resected the primary focus in an orthotopic implantation model to examine when metastasis of cancer cells occurs. Human squamous cell carcinoma was implanted to the tongue of nude mice divided into two groups, a non-surgery and a surgery group. Mice of the first group were sacrificed 3, 7, 14, 21 or 28 days postimplantation, and the tongue tumor and cervical lymph nodes were resected simultaneously. On the mice of the second group, resection of the tongue tumor was performed on days 3, 7 or 14, and the cervical lymph nodes were resected on day 28. The incidence of metastasis in the two groups was then compared. For the non-surgery group, the incidence of metastasis was 0% on day 3, 9% on day 7, 36% on day 14, 91% on day 21 and 100% on day 28. When resection of the tongue tumor was performed on days 3, 7 and 14, the incidence of metastasis for the surgery group at 28 days was 0%, 82% and 91%, respectively. Therefore, the proportion of mice with occult metastasis was the highest in the group, in which there was no metastasis and only the local tumor was resected on day 7, but metastasis was detected thereafter. These findings suggest that this period corresponds to the initial stage of metastasis. This time-based model may therefore be useful for clarifying the mechanism of metastasis and for the development of new treatments.