Enhanced metastatic growth after local tumor resection in the presence of synchronous metastasis in a mouse allograft model of neuroblastoma

Abstract

Purpose: We investigated how local tumor resection affects metastatic lesions in neuroblastoma.

Methods: MYCN Tg tumor-derived cells were injected subcutaneously into 129^+Ter/SvJcl wild-type mice. First, the frequency of metastasis-bearing mice was investigated immunohistochemically (metastatic ratio) at endpoint or post-injection day (PID) 90. Second, the threshold volume of local tumor in mice bearing microscopic lymph node metastasis (mLNM) was investigated at PID 30. Finally, local tumors were resected after exceeding the threshold. Mice were divided into local tumor resection (Resection) and observation (Observation) groups, and the metastatic ratio and volume of LNM were compared between the groups at endpoint or PID 74.

Results: The metastatic ratio without local resection was 88% at PID 78-90. The threshold local tumor volume in the mice with mLNM was 745 mm³ at PID 30, so local tumors were resected after exceeding 700 mm³. The metastatic ratio and LNM volume were significantly greater in the Resection group (n = 16) than in the Observation group (n = 16) (94% vs. 38%, p < 0.001; 2092 ± 2310 vs. 275 ± 218 mm³, p < 0.01; respectively) at PID 50-74.

Conclusion: Local tumor resection might augment the growth of synchronous microscopic metastases. Our results provide insights into the appropriate timing of local resection for high-risk neuroblastoma.

Keywords: Concomitant tumor resistance; Local tumor resection; MYCN transgenic mouse; Metastasis; Neuroblastoma.