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Splenectomy reduces lung metastases and tumoral and metastatic niche inflammation.
Stöth, Manuel; Freire Valls, Aida; Chen, Mingyi; Hidding, Sarah; Knipper, Karl; Shen, Ying; Klose, Johannes; Ulrich, Alexis; Ruiz de Almodovar, Carmen; Schneider, Martin; Schmidt, Thomas.
Afiliación
  • Stöth M; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Freire Valls A; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Chen M; Biochemistry Center (BZH), University of Heidelberg, Heidelberg, Germany.
  • Hidding S; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Knipper K; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Shen Y; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Klose J; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Ulrich A; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Ruiz de Almodovar C; Department of General, Visceral, and Transplantation Surgery, University Hospital of Heidelberg, Heidelberg, Germany.
  • Schneider M; Biochemistry Center (BZH), University of Heidelberg, Heidelberg, Germany.
  • Schmidt T; European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Int J Cancer ; 145(9): 2509-2520, 2019 11 01.
Article en En | MEDLINE | ID: mdl-31034094
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bazo / Inflamación / Pulmón / Neoplasias Pulmonares / Metástasis Linfática Límite: Animals Idioma: En Revista: Int J Cancer Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bazo / Inflamación / Pulmón / Neoplasias Pulmonares / Metástasis Linfática Límite: Animals Idioma: En Revista: Int J Cancer Año: 2019 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos