Enhanced metastatic growth after local tumor resection in the presence of synchronous metastasis in a mouse allograft model of neuroblastoma
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We investigated how local tumor resection affects metastatic lesions in neuroblastoma.
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.
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.
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.
KeywordsNeuroblastoma Metastasis Local tumor resection Concomitant tumor resistance MYCN transgenic mouse
This work was supported in part by Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI grant number 18H02600 [KY], 16K19008 [YU] and 15H05000 [TT]). The English used in this manuscript was reviewed by Brian Quinn (Editor-in-Chief, Japan Medical Communication).
Compliance with ethical standards
Conflict of interest
The authors declare no conflicts of interest in association with the present study.
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