Decreased Growth Rate of Lung Metastatic Lesions after Splenectomy in Mice

Sonoda, Kazuya; Izumi, Koichi; Matsui, Yoko; Ito, Masafumi; Shiraishi, Norio; Kitano, Seigo

doi:10.1159/000095415

Cited by 14 publications

(10 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it causes smaller and fewer hematogenous breast cancer lung metastases. In line, in a subcutaneously inoculated lung cancer and in a colorectal CT26 tail vein injection model, splenectomy also reduced the number of lung metastases. In contrast, splenectomy in a portal vein injection model using the same CT26 tumor cell line caused a higher number of liver metastases, instead of its inhibition.…”

Section: Discussionsupporting

confidence: 91%

“…The literature on the role of splenectomy in tumor progression and metastasis remains inconclusive. There are studies showing that splenectomy plays a role in (i) promoting [16][17][18][19] or (ii) inhibiting tumor growth and metastasis 10,11,[20][21][22][23][24][25] or (iii) not influencing tumor progression at all 26 ; highlighting its multifaceted role during malignant development. In the present study, splenectomy did not affect growth of primary Panc02, 4T1 and E0771 tumors.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Stöth

Valls

Chen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

The immune microenvironment plays a crucial role in supporting tumor growth and metastasis. Tumor‐associated macrophages (TAMs) and neutrophils (TANs) are essential components of this microenvironment and affect tumor growth and progression in almost all solid neoplasms. Furthermore, TAMs, TANs and tumor‐infiltrating dendritic cells (TIDCs) are found to infiltrate specific distant organs to prepare them as a site for metastatic cell seeding, forming the pre‐metastatic niche. The spleen was identified as a major reservoir and source of circulating and tumor infiltrating immune cells. However, discrepancies about its role in supporting tumor growth exist. Thus, here we investigated the role of splenectomy in primary tumor and metastatic growth, and in the formation of an inflammatory niche. In a murine 4T1 and E0771 breast and Panc02 pancreatic cancer model, our results show that while splenectomy reduces the number of infiltrating TAMs, TANs and TIDCs within primary tumors, it does not affect its growth. In line, fewer TAMs, TANs and TIDCs accumulate in the metastatic microenvironment after splenectomy. Interestingly though, this affected metastatic growth depending on the metastatic route/site. The number of hematogenous breast cancer lung metastases was reduced after splenectomy but no effect was observed in breast or pancreatic lymph node metastases. Moreover, we observed that the immune composition of the pre‐metastatic niche in lungs of breast cancer bearing mice was altered, and that this could cause the reduction of metastases. Altogether, our results highlight that splenectomy affects the immune microenvironment not only of primary tumors but also of pre‐metastatic and metastatic sites.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Stöth

Valls

Chen

et al. 2019

Intl Journal of Cancer

View full text Add to dashboard Cite

show abstract

“…The spleen, a secondary lymphoid organ, may be involved in the anti-tumour immune response, and a relationship between splenectomy and lung metastasis has been reported (31,32). We noticed that at 12 days after inoculation, the percentage and absolute number of CD3 + T cells were significantly increased in the spleen.…”

Section: Discussionmentioning

confidence: 52%

Decreased NK cell cytotoxicity and increased T regulatory cells facilitate progression of metastatic murine melanoma

Radosavljević¹,

Jovanović²,

Martinova³

et al. 2012

Ser J Exp Clin Res

View full text Add to dashboard Cite

Malignant melanoma is the most aggressive form of skin cancer. Metastatic dissemination in distant organs is one of the hallmarks of melanoma progression. Immunosuppression and tumour escape from immune surveillance are thought to be the major factors responsible for the establishment and progression of melanoma; however, the exact mechanisms leading to decreased anti-tumour immunity are not completely understood. We aimed to analyse the anti-tumour immune response during hematogenous metastasis using a B16-F1 metastatic melanoma model in C57BL/6 mice. At 21 days after tumour cell inoculation, rapid metastatic melanoma growth was observed, reflected through the increased incidence, number and size of metastatic colonies in the lungs (B16-F1). Phenotypic analyses of splenocytes revealed an increased percentage of CD3 + T cells, a markedly reduced percentage of CD19 + B cells and an increased percentage and absolute number of CD4 + Foxp3 + T regulatory cells. The cytotoxic activities of total splenocytes and isolated NK cells were significantly decreased in tumour-bearing mice. Thus, the metastatic progression of melanoma in this model is associated with diminished NK cytotoxicity, which may be due to an increased expansion of suppressive CD4 + Foxp3 + T regulatory cells in the spleen.

show abstract

“…Splenectomy has been reported to serve an important role in the antitumor immune response in an experimental model (27)(28)(29). Higashijima et al (28) reported that splenectomy enhances liver metastasis through an increase in forkhead box P3 mRNA in the liver.…”

Section: Univariate Analysismentioning

confidence: 99%

“…Higashijima et al (28) reported that splenectomy enhances liver metastasis through an increase in forkhead box P3 mRNA in the liver. On the other hand, Sonoda et al (29) reported that the metastatic lung nodules were significantly smaller in size and number in the subject group that underwent splenectomy compared with the control group in a mouse metastasis model and concluded that this occurred due to splenectomy-induced decreases in serum levels of vascular endothelial growth factor and basic fibroblast growth factor. In the present study, patients with (y)pT3N0 EGJ cancer who underwent splenectomy had improved DSS compared with those who did not undergo splenectomy.…”

Section: Univariate Analysismentioning

confidence: 99%

Prognoses of advanced esophago‑gastric junction cancer may be modified by thoracotomy and splenectomy

et al. 2017

View full text Add to dashboard Cite

Abstract. Globally, the incidence of esophago-gastric junction (EGJ) cancer is rapidly increasing. However, the proposed strategies for the treatment of these types of cancer are so diverse that there is no established consensus on the optimal treatment. The aim of the present study was to identify independent prognostic factors to delineate the optimal strategies for the treatment of EGJ cancer. The medical records of 150 patients with EGJ cancer who underwent curative surgery at the Kitasato University were retrospectively reviewed. The median follow-up period was 48 months. The patients with tumors that were classified as post-treatment primary tumor stage 3 [(y)pT3] or higher had a 5-year disease-specific survival (DSS) rate of 53%, whereas those with tumors that were classified as (y)pT0-2 had a 5-year DSS rate of 90%. Therefore, prognostic analysis was restricted to those tumors that were designated (y)pT3 or higher. A multivariate Cox's proportional hazards model identified the following independent prognostic factors that negatively influenced the DSS: i) Presence of tumors classified as post-treatment regional lymph node stage 1-3 [(y)pN1-3] [hazard ratio (HR), 3.62; 95% confidence interval (CI), 1.39-12.36]; ii) not undergoing treatment with splenectomy (HR, 2.40; 95% CI, 1.15-5.15); and iii) undergoing treatment with thoracotomy (HR, 2.07; 95% CI, 1.02-4.23). In patients with (y)pN0 tumors, the DSS rate was significantly improved for those who underwent splenectomy than for those who did not (P=0.024). In patients with (y)pN1-3 tumors, the DSS rate was significantly worse for those who underwent thoracotomy compared with those who did not (P=0.004). Splenectomy and thoracotomy may critically affect prognosis in locally advanced EGJ cancer that are classified as (y)pN0 and (y)pN1-3, respectively. Surgical treatments require optimization in order to improve prognoses in advanced EGJ cancer.

show abstract

Decreased Growth Rate of Lung Metastatic Lesions after Splenectomy in Mice

Cited by 14 publications

References 53 publications

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation

Decreased NK cell cytotoxicity and increased T regulatory cells facilitate progression of metastatic murine melanoma

Prognoses of advanced esophago‑gastric junction cancer may be modified by thoracotomy and splenectomy

Contact Info

Product

Resources

About