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Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells
Open accessAbstract
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.
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Cites
Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH
Heuser, J. (1989) · The Journal of cell biology · doi:10.1083/jcb.108.3.855 · Cited by 390
Cited by
Lysosomes as dynamic regulators of cell and organismal homeostasis
Ballabio, A., & Bonifacino, J. S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0185-4 · Cited by 1,469
Lysosomal membrane permeabilization in cell death
Boya, P., & Kroemer, G. (2008) · Oncogene · doi:10.1038/onc.2008.310 · Cited by 1,426
Tumour acidosis: from the passenger to the driver's seat
Corbet, C., & Feron, O. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2017.77 · Cited by 988
The role of disturbed pH dynamics and the Na+/H+ exchanger in metastasis
Cardone, R. A., Casavola, V., & Reshkin, S. J. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1713 · Cited by 897
Acid-Mediated Tumor Invasion: a Multidisciplinary Study
Gatenby, R. A., Gawlinski, E. T., Gmitro, A. F., Kaylor, B., & Gillies, R. J. (2006) · Cancer Research · doi:10.1158/0008-5472.can-05-4193 · Cited by 771
Metadata
- Authors
- Glunde, K., Guggino, S. E., Solaiyappan, M., Pathak, A. P., Ichikawa, Y., & Bhujwalla, Z. M.
- Venue
- Neoplasia
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 5
- Issue
- 6
- Pages
- 533-545
- ISSN
- 1476-5586 (ISSN-L)
- OpenAlex
- W2040340572
- Cited by
- 285
- References
- 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- gold
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- Glunde, K., Guggino, S. E., Solaiyappan, M., Pathak, A. P., Ichikawa, Y., & Bhujwalla, Z. M. (2003). Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells. Neoplasia. https://doi.org/10.1016/s1476-5586(03)80037-4
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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