Vincan Elizabeth, Brabletz Thomas, Faux Maree C, Ramsay Robert G
Research Division, Peter MacCallum Cancer Centre, Melbourne, Australia.
Cells Tissues Organs. 2007;185(1-3):20-8. doi: 10.1159/000101299.
Developmental morphogenesis relies on cell transitions between epithelial and mesenchymal states. Colorectal cancer (CRC) progression can also be described as 'morphogenesis' as it involves epithelial-mesenchymal transition (EMT), whereby tumour cells become more invasive and metastatic. Subsequently, the disseminated tumour cells must undergo a reverse transition (MET), as the pathology of most primary tumours is re-capitulated by their established metastases. Disseminated tumour cells can remain 'dormant' for many years. Consequently, tumour initiation at the secondary site is the rate-limiting step in metastasis. Metastasis is governed by cell intrinsic and extrinsic (microenvironment) factors, thus much of what we know about metastasis is drawn from in vivo model systems. However, the molecular mechanisms controlling release from 'dormancy' are still largely unknown due to the complexity this presents for the in vivo situation. An in vitro morphogenesis culture system would present a great advantage. To this end, we have established a unique model of CRC morphogenesis, using a variant of the human cell line LIM1863 (LIM1863-Mph). In this model system LIM1863-Mph cells show plasticity between epithelial and mesenchymal states. The transitions are reversible and bear the phenotypic hallmarks of CRC morphogenesis. Importantly, we have demonstrated a pivotal role for FZD7 in these phenotype transitions, implicating Wnt signalling in orchestrating CRC morphogenesis.
发育形态发生依赖于上皮和间充质状态之间的细胞转变。结直肠癌（CRC）的进展也可被描述为“形态发生”，因为它涉及上皮-间质转化（EMT），在此过程中肿瘤细胞变得更具侵袭性和转移性。随后，播散的肿瘤细胞必须经历逆向转变（MET），因为大多数原发性肿瘤的病理特征会在其已形成的转移灶中重现。播散的肿瘤细胞可以“休眠”多年。因此，肿瘤在继发部位的起始是转移中的限速步骤。转移受细胞内在和外在（微环境）因素的控制，因此我们对转移的许多了解都来自体内模型系统。然而，由于体内情况的复杂性，控制从“休眠”中释放的分子机制仍 largely 未知。体外形态发生培养系统将具有很大优势。为此，我们建立了一种独特的 CRC 形态发生模型，使用人类细胞系 LIM1863 的一个变体（LIM1863-Mph）。在这个模型系统中，LIM1863-Mph 细胞在上皮和间充质状态之间表现出可塑性。这些转变是可逆的，并具有 CRC 形态发生的表型特征。重要的是，我们已经证明 FZD7 在这些表型转变中起关键作用，这表明 Wnt 信号在协调 CRC 形态发生中起作用。 （注：“largely”原英文表述有误，推测可能是“largely”，翻译为“很大程度上” ）
