Desoize B, Gimonet D, Jardillier J C
IFR 53-EA 2063, Faculté de pharmacie, Reims.
Bull Cancer. 1998 Sep;85(9):785-93.
Cells cultured as spheroids present an heterogeneity similar to that of tumours in vivo. In the spheroid peripheral layers, cells are proliferating, deeper cells are non-cycling, when in the aggregate centre, cells from often a necrotic core. A multicellular resistance appears in spheroids, it is a result of the cell contact to other cells (homogeneous or heterogeneous cells) and/or to the extracellular matrix. The mechanism of this resistance is not known, nevertheless, it can be hypothesised to be linked to the spheroid centre hypoxia, to the quiescence of a large fraction of the cell population and to the apoptosis inhibition due to the cell contact. The "classical" or "unicellular" mechanisms of resistance, as mdr1, MRP, can coexist with the multicellular resistance, but are not responsible for this resistance. The spheroid model of culture is a good opportunity to study a resistance type which looks close to the tumour resistance found in vivo in mice and in patients. A new class of therapeutic molecules appears that can reverse this multicellular resistance, inhibit tumours growth and preclude metastases. The principal mechanism of action of this new pharmacological class appears to be the disruption of the intercellular adhesion forces. Preliminary results obtained with these compounds in patients are promising.
作为球体培养的细胞呈现出与体内肿瘤相似的异质性。在球体的外周层，细胞在增殖，更深层的细胞处于非循环状态，而在聚集体中心，细胞常常形成坏死核心。球体中出现了多细胞耐药性，这是细胞与其他细胞（同种或异种细胞）和/或细胞外基质接触的结果。这种耐药性的机制尚不清楚，不过，可以推测它与球体中心的缺氧、大部分细胞群体的静止状态以及细胞接触导致的凋亡抑制有关。“经典”或“单细胞”耐药机制，如mdr1、MRP，可与多细胞耐药性共存，但并非这种耐药性的原因。球体培养模型是研究一种与在小鼠和患者体内发现的肿瘤耐药性相似的耐药类型的好机会。一类新的治疗分子出现了，它们可以逆转这种多细胞耐药性、抑制肿瘤生长并防止转移。这类新药理学类别的主要作用机制似乎是破坏细胞间粘附力。在患者中使用这些化合物获得的初步结果很有前景。
