Mast cells impair melanoma cell homing and metastasis by inhibiting HMGA1 secretion

Autor: Alberto Benito‐Martin, Laura Nogués, Marta Hergueta‐Redondo, Elena Castellano‐Sanz, Eduardo Garvin, Michele Cioffi, Paloma Sola‐Castrillo, Weston Buehring, Pilar Ximénez‐Embún, Javier Muñoz, Irina Matei, Josep Villanueva, Héctor Peinado
Přispěvatelé: Institut Català de la Salut, [Benito-Martin A] Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health and the Meyer Cancer Center, Weill Cornell Medical College, New York, New York, USA. Universidad Alfonso X El Sabio, Facultad de Medicina, Unidad de Investigacion Biomédica, Madrid, Spain. [Nogués L] Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health and the Meyer Cancer Center, Weill Cornell Medical College, New York, New York, USA. Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain. [Hergueta-Redondo M, Castellano-Sanz E, Garvin E] Microenvironment and Metastasis Laboratory, Molecular Oncology Program, Spanish National Cancer Research Center (CNIO), Madrid, Spain. [Cioffi M] Children’s Cancer and Blood Foundation Laboratories, Departments of Pediatrics, and Cell and Developmental Biology, Drukier Institute for Children’s Health and the Meyer Cancer Center, Weill Cornell Medical College, New York, New York, USA. [Villanueva J] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2022
Předmět:
Zdroj: Scientia
ISSN: 1365-2567
Popis: Mast cells; Melanoma; Metastasis Mastòcits; Melanoma; Metàstasi Mastocitos; Melanoma; Metástasis Metastatic disease is the major cause of death from cancer. From the primary tumour, cells remotely prepare the environment of the future metastatic sites by secreted factors and extracellular vesicles. During this process, known as pre-metastatic niche formation, immune cells play a crucial role. Mast cells are haematopoietic bone marrow-derived innate immune cells whose function in lung immune response to invading tumours remains to be defined. We found reduced melanoma lung metastasis in mast cell-deficient mouse models (Wsh and MCTP5-Cre-RDTR), supporting a pro-metastatic role for mast cells in vivo. However, due to evidence pointing to their antitumorigenic role, we studied the impact of mast cells in melanoma cell function in vitro. Surprisingly, in vitro co-culture of bone-marrow-derived mast cells with melanoma cells showed that they have an intrinsic anti-metastatic activity. Mass spectrometry analysis of melanoma-mast cell co-cultures secretome showed that HMGA1 secretion by melanoma cells was significantly impaired. Consistently, HMGA1 knockdown in B16-F10 cells reduced their metastatic capacity in vivo. Importantly, analysis of HMGA1 expression in human melanoma tumours showed that metastatic tumours with high HMGA1 expression are associated with reduced overall and disease-free survival. Moreover, we show that HMGA1 is reduced in the nuclei and enriched in the cytoplasm of melanoma metastatic lesions when compared to primary tumours. These data suggest that high HMGA1 expression and secretion from melanoma cells promote metastatic behaviour. Targeting HMGA1 expression intrinsically or extrinsically by mast cells actions reduce melanoma metastasis. Our results pave the way to the use of HMGA1 as anti-metastatic target in melanoma as previously suggested in other cancer types. US NIH (R01-CA169416); Children's Cancer and Blood Foundation; Feldestein Foundation; Melanoma Research Alliance; Nancy C. and Daniel P. Paduano Foundation; Starr Foundation; Translational NeTwork for the CLinical application of Extracellular VesicleS
Databáze: OpenAIRE
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