Development of in vitro models of common cancers of the urological system to investigate the effects on the tumour microenvironment

细胞微环境（包括基质刚性、可溶性因子、细胞-细胞和细胞-细胞外基质（ECM）相互作用）有助于癌细胞对治疗的反应。肿瘤和周围组织中的低氧张力（缺氧）大大降低了前列腺癌和膀胱癌患者的放射治疗效果。与单层培养相比，3D培养的癌细胞可以在更高程度上重现体内肿瘤。在3D中培养的肿瘤细胞的增殖通常较慢，因此比单层培养物的增殖更具有生理相关性。在这个项目中，我们将开发3D肿瘤模型，以更好地再现肿瘤微环境，并改善癌症治疗方式的体外评估。我们已经建立了纤维支架和3D癌症模型，使用合成（自组装肽）和天然（藻酸盐，胶原蛋白）水凝胶，更好地模拟肿瘤的纤维成分。在这里，我们的目标是开发3D模型与肿瘤细胞接种在生物材料之间的桥梁，在平面二维体外培养和体内实验之间的差距。这些细胞将在具有可调节的氧气输送的灌注生物反应器中培养，或者在缺氧诱导剂的存在下培养，以模拟实体瘤中观察到的缺氧环境，从而使我们能够评估缺氧在治疗抗性中的作用，更具体地说，在辐射反应中。

The cellular microenvironment (which includes matrix rigidity, soluble factors, cell-cell and cell-extracellular matrix (ECM) interactions) is instrumental to the response of cancer cells to treatment. Low oxygen tension (hypoxia) within the tumour and surrounding tissues greatly reduces the effectiveness of radiotherapy for prostate and bladder cancer patients.Cancer cells cultured in 3D can recapitulate the in vivo tumours to a significantly higher degree when compared to monolayer cultures. The proliferation of tumour cells cultured in 3D is typically slower and hence more physiologically relevant than that of monolayer cultures. In this project 3D tumour models will be developed that better recapitulate the tumour microenvironment and improve the in vitro assessment of cancer therapeutics modalities.We have established fibrous scaffolds and 3D cancer models using synthetic (self-assembling peptides) and natural (alginate, collagen) hydrogels that better mimic the fibrous component of tumours. Here, we aim to develop 3D models with tumour cells seeded within the biomaterials to bridge the gap between flat 2D in vitro culture and in vivo experiments. These will be cultured in a perfusion bioreactor with modifiable oxygen delivery or in the presence of hypoxia inducers to mimic the hypoxic environment seen in solid tumours to allow us to assess the role of hypoxia in treatment resistance, and more specifically in radiation response.