A 3D model of tumour angiogenic microenvironment to monitor hypoxia effects on cell interactions and cancer stem cell selection

• Published in: Cancer letters Vol. 396; pp. 10 - 20
• Main Authors: Klimkiewicz, Krzysztof, Weglarczyk, Kazimierz, Collet, Guillaume, Paprocka, Maria, Guichard, Alan, Sarna, Michal, Jozkowicz, Alicja, Dulak, Jozef, Sarna, Tadeusz, Grillon, Catherine, Kieda, Claudine
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28.06.2017; Elsevier Limited; Elsevier
• Subjects: Adhesion; AKT protein; Aldehyde dehydrogenase; Angiogenesis; Animal models; Animals; Atmosphere; Blood; Bone marrow; Brain tumors; Cancer therapies; Carbon dioxide; Carcinogenesis; CCL21 protein; Cell adhesion molecules; Cell Communication - physiology; Cell Hypoxia - physiology; Cell interactions; Cell Proliferation - physiology; Chemokine receptors; Chemokines; Cloning; Culture; Cytokines; Dehydrogenase; Deoxyribonucleic acid; DNA; Endothelial progenitors; Evaluation; Hematology, Oncology and Palliative Medicine; Humans; Hypoxia; Imaging, Three-Dimensional; Labeling; Life Sciences; Lungs; Lymph nodes; Melanoma; Melanoma - blood supply; Melanoma - metabolism; Melanoma - pathology; Melanoma, Experimental - blood supply; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Metastases; Metastasis; Mice; microRNA; Mimicry; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Plates (structural members); Reconstruction; Recruitment; Skin; Solar radiation; Spheroid tumour model; Spheroids, Cellular; Statistical analysis; Stem cells; Tracers; Tumor Microenvironment; Tumors; Typing; Ultraviolet radiation; Angiogenesis; hypoxia; spheroid tumour model; endothelial progenitors; recruitment; micro-RNA; Spheroid tumour model; Hypoxia; microRNA; Endothelial progenitors; Recruitment; Spheroid tumour model microRNA
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.03.006

Abstract Tumour microenvironment determines the fate of treatments. Reconstitution of tumour conditions is mandatory for alternative in vitro methods devoted to cancer development and the selection of therapeutic strategies. This work describes a 3D model of melanoma growth in its environment. Introducing means to mimic tumour angiogenesis, which turns on tumour progression, the model shows that melanoma tumour spheroids allow reconstitution of solid tumours with stromal cells. Angiogenesis evidenced the differential recruitment of endothelial cells (EC) from early progenitors (EEPCs) to mature ECs. Hypoxia was the key parameter that selected and stabilized melanoma cancer stem like cells (CSCs) phenotype based on aldehyde dehydrogenase expression as the best criterion. The 3D-tumour-model demonstrated the distinct reactivity of ECs toward tumour cells in terms of cellular cross-talk and humoral response. Intra-spheroid cell-to-cell membrane dye exchanges, mediated by intercellular interactions, uncovered the melanoma-to-EEPC cooperation. The resulting changes in tumour milieu were evidenced by the chemokinic composition and hypoxia-related variations in microRNA expression assessed in each cellular component of the spheroids. This method brings new tools to decipher the molecular mechanism of tumour-mediated cell recruitment and for in vitro assessment of therapeutic approaches.