Department of Molecular Pathology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, 1066 CX, the Netherlands.
Department of Molecular Pathology, Oncode Institute, Netherlands Cancer Institute, Amsterdam, 1066 CX, the Netherlands.
Dev Cell. 2023 Apr 10;58(7):535-549.e5. doi: 10.1016/j.devcel.2023.02.017. Epub 2023 Mar 10.
The basement membrane (BM) around tumor lobes forms a barrier to prevent cancer cells from invading the surrounding tissue. Although myoepithelial cells are key producers of the healthy mammary epithelium BM, they are nearly absent in mammary tumors. To study the origin and dynamics of the BM, we developed and imaged a laminin beta1-Dendra2 mouse model. We show that the turnover of laminin beta1 is faster in the BMs that surround the tumor lobes than in the BMs that surround the healthy epithelium. Moreover, we find that epithelial cancer cells and tumor-infiltrating endothelial cells synthesize laminin beta1 and that this production is temporarily and locally heterogeneous, leading to local discontinuity of the BM laminin beta1. Collectively, our data draw a new paradigm for tumor BM turnover in which the disassembly happens at a constant rate, and a local misbalance of compensating production leads to reduction or even complete disappearance of the BM.
肿瘤小叶周围的基底膜（BM）形成一道屏障，防止癌细胞侵入周围组织。虽然肌上皮细胞是健康乳腺上皮 BM 的主要产生者，但它们在乳腺肿瘤中几乎不存在。为了研究 BM 的起源和动态，我们开发并成像了一个层粘连蛋白β1-Dendra2 小鼠模型。我们发现，肿瘤小叶周围的 BM 中层粘连蛋白β1 的周转率比健康上皮周围的 BM 快。此外，我们发现上皮癌细胞和肿瘤浸润的内皮细胞合成层粘连蛋白β1，并且这种产生是暂时和局部不均匀的，导致 BM 层粘连蛋白β1 的局部不连续性。总的来说，我们的数据为肿瘤 BM 周转率描绘了一个新的范例，其中解组装以恒定的速率发生，局部补偿产生的不平衡导致 BM 的减少甚至完全消失。
