Hamilton G
Ludwig Boltzmann Institute of Clinical Oncology, KH Lainz, Vienna, Austria.
Cancer Lett. 1998 Sep 11;131(1):29-34. doi: 10.1016/s0304-3835(98)00198-0.
Multicellular spheroids (MCS) have been used as an in vitro model system of micrometastases and avascular tumor regions for studying cell adhesion-dependent resistance to cytotoxic drugs and possible reversal by chemosensitizers and adhesion-reversing agents. Multicellular drug resistance has been linked to limited accessibility of cell subpopulations, active drug efflux, quiescence of cells in deeper layers due to cell contact inhibition and adverse microenvironmental conditions like acidic extracellular pH, hypoxia and nutritional depletion. The shortcomings of MCS as a tumor model include limited knowledge of the mechanisms leading to necrosis/apoptosis of core cells, the production of an extracellular matrix (ECM) by tumor cells instead of intratumoral normal cell populations and the complex relationship of MCS parameters like size, growth regulation, synthesis of ECM components and others on the origin and pretreatment of the tumor cells and specific culture conditions.
多细胞球体（MCS）已被用作微转移和无血管肿瘤区域的体外模型系统，用于研究细胞黏附依赖性的细胞毒性药物抗性以及化学增敏剂和黏附逆转剂的可能逆转作用。多细胞耐药性与细胞亚群的有限可及性、活性药物外排、由于细胞接触抑制导致深层细胞的静止以及酸性细胞外pH、缺氧和营养耗竭等不利微环境条件有关。MCS作为肿瘤模型的缺点包括对导致核心细胞坏死/凋亡的机制了解有限、肿瘤细胞而非肿瘤内正常细胞群体产生细胞外基质（ECM）以及MCS参数（如大小、生长调节、ECM成分合成等）与肿瘤细胞的起源和预处理以及特定培养条件之间的复杂关系。
