HIF-1α regulates the interaction of chronic lymphocytic leukemia cells with the tumor microenvironment
| Autor: | Maria Teresa Sabrina Bertilaccio, Federico Caligaris-Cappio, Manfredi Ponente, Paola Brambilla, Giovanni Tonon, Rosa Bernardi, Elisabetta Ferrero, Filippo Martinelli Boneschi, Paolo Ghia, Maurilio Ponzoni, Marina Ferrarini, Andrea Brendolan, Elisa Lenti, Elisa Ten Hacken, Lydia Scarfò, Cristina Scielzo, Daniela Belloni, Roberta Valsecchi, Nadia Coltella |
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| Přispěvatelé: | Valsecchi, Roberta, Coltella, Nadia, Belloni, Daniela, Ponente, Manfredi, Ten Hacken, Elisa, Scielzo, Cristina, Scarfò, Lydia, Bertilaccio, Maria Teresa Sabrina, Brambilla, Paola, Lenti, Elisa, Boneschi, Filippo Martinelli, Brendolan, Andrea, Ferrero, Elisabetta, Ferrarini, Marina, Ghia, PAOLO PROSPERO, Tonon, Giovanni, Ponzoni, Maurilio, CALIGARIS CAPPIO, Federico, Bernardi, Rosa |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stromal cell Chronic lymphocytic leukemia Immunology Mice Transgenic Cell Communication Biology Biochemistry 03 medical and health sciences Chemokine receptor Mice 0302 clinical medicine HEK293 Cell immune system diseases Bone Marrow hemic and lymphatic diseases medicine Cell Adhesion Tumor Microenvironment Animals Humans Cell adhesion neoplasms Tumor microenvironment Lymphoid Neoplasia Cell adhesion molecule Animal Gene Expression Regulation Leukemic Stromal Cell Hematology Cell Biology medicine.disease Hypoxia-Inducible Factor 1 alpha Subunit Leukemia Lymphocytic Chronic B-Cell Cell biology Mice Inbred C57BL Leukemia Chemotaxis Leukocyte 030104 developmental biology medicine.anatomical_structure HEK293 Cells 030220 oncology & carcinogenesis Bone marrow Stromal Cells Spleen Human |
| Popis: | Hypoxia-inducible transcription factors (HIFs) regulate a wide array of adaptive responses to hypoxia and are often activated in solid tumors and hematologic malignancies due to intratumoral hypoxia and emerging new layers of regulation. We found that in chronic lymphocytic leukemia (CLL), HIF-1α is a novel regulator of the interaction of CLL cells with protective leukemia microenvironments and, in turn, is regulated by this interaction in a positive feedback loop that promotes leukemia survival and propagation. Through unbiased microarray analysis, we found that in CLL cells, HIF-1α regulates the expression of important chemokine receptors and cell adhesion molecules that control the interaction of leukemic cells with bone marrow and spleen microenvironments. Inactivation of HIF-1α impairs chemotaxis and cell adhesion to stroma, reduces bone marrow and spleen colonization in xenograft and allograft CLL mouse models, and prolongs survival in mice. Of interest, we found that in CLL cells, HIF-1α is transcriptionally regulated after coculture with stromal cells. Furthermore, HIF-1α messenger RNA levels vary significantly within CLL patients and correlate with the expression of HIF-1α target genes, including CXCR4, thus further emphasizing the relevance of HIF-1α expression to CLL pathogenesis. |
| Databáze: | OpenAIRE |
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