Glunde Kristine, Guggino Sandra E, Solaiyappan Meiyappan, Pathak Arvind P, Ichikawa Yoshitaka, Bhujwalla Zaver M
Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neoplasia. 2003 Nov-Dec;5(6):533-45. doi: 10.1016/s1476-5586(03)80037-4.
Cancer cells invade by secreting degradative enzymes, which are sequestered in lysosomal vesicles. In this study, the impact of an acidic extracellular environment on lysosome size, number, and distance from the nucleus in human mammary epithelial cells (HMECs) and breast cancer cells of different degrees of malignancy was characterized because the physiological microenvironment of tumors is frequently characterized by extracellular acidity. An acidic extracellular pH (pH(e)) resulted in a distinct shift of lysosomes from the perinuclear region to the cell periphery irrespective of the HMECs' degree of malignancy. With decreasing pH, larger lysosomal vesicles were observed more frequently in highly metastatic breast cancer cells, whereas smaller lysosomes were observed in poorly metastatic breast cancer cells and HMECs. The number of lysosomes decreased with acidic pH values. The displacement of lysosomes to the cell periphery driven by extracellular acidosis may facilitate exocytosis of these lysosomes and increase secretion of degradative enzymes. Filopodia formations, which were observed more frequently in highly metastatic breast cancer cells maintained at acidic pH(e), may also contribute to invasion.
癌细胞通过分泌隔离于溶酶体小泡中的降解酶来实现侵袭。在本研究中，鉴于肿瘤的生理微环境常以细胞外酸性为特征，因此对酸性细胞外环境对人乳腺上皮细胞（HMECs）以及不同恶性程度乳腺癌细胞中溶酶体大小、数量及与细胞核距离的影响进行了表征。细胞外酸性pH值（pH(e)）导致溶酶体从核周区域明显转移至细胞周边，而与HMECs的恶性程度无关。随着pH值降低，在高转移性乳腺癌细胞中更频繁地观察到更大的溶酶体小泡，而在低转移性乳腺癌细胞和HMECs中观察到的是较小的溶酶体。溶酶体的数量随着酸性pH值而减少。细胞外酸中毒驱动溶酶体向细胞周边的移位可能会促进这些溶酶体的胞吐作用，并增加降解酶的分泌。在维持于酸性pH(e)的高转移性乳腺癌细胞中更频繁观察到的丝状伪足形成，也可能有助于侵袭。
