Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells
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 d...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2003-11-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558603800374 |
| _version_ | 1819027539523272704 |
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| author | Kristine Glunde Sandra E. Guggino Meiyappan Solaiyappan Arvind P. Pathak Yoshitaka Ichikawa Zaver M. Bhujwalla |
| author_facet | Kristine Glunde Sandra E. Guggino Meiyappan Solaiyappan Arvind P. Pathak Yoshitaka Ichikawa Zaver M. Bhujwalla |
| author_sort | Kristine Glunde |
| collection | DOAJ |
| description | 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 (pHe) 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 pHe, may also contribute to invasion. |
| first_indexed | 2024-12-21T05:44:05Z |
| format | Article |
| id | doaj.art-b4f4624b416c45c393d8945c1728f24a |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-21T05:44:05Z |
| publishDate | 2003-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-b4f4624b416c45c393d8945c1728f24a2022-12-21T19:14:10ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022003-11-015653354510.1016/S1476-5586(03)80037-4Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer CellsKristine Glunde0Sandra E. Guggino1Meiyappan Solaiyappan2Arvind P. Pathak3Yoshitaka Ichikawa4Zaver M. Bhujwalla5Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USADepartment of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USACancer 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 (pHe) 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 pHe, may also contribute to invasion.http://www.sciencedirect.com/science/article/pii/S1476558603800374Breast cancermetastasisfluorescence microscopylysosometrafficking |
| spellingShingle | Kristine Glunde Sandra E. Guggino Meiyappan Solaiyappan Arvind P. Pathak Yoshitaka Ichikawa Zaver M. Bhujwalla Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells Neoplasia: An International Journal for Oncology Research Breast cancer metastasis fluorescence microscopy lysosome trafficking |
| title | Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells |
| title_full | Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells |
| title_fullStr | Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells |
| title_full_unstemmed | Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells |
| title_short | Extracellular Acidification Alters Lysosomal Trafficking in Human Breast Cancer Cells |
| title_sort | extracellular acidification alters lysosomal trafficking in human breast cancer cells |
| topic | Breast cancer metastasis fluorescence microscopy lysosome trafficking |
| url | http://www.sciencedirect.com/science/article/pii/S1476558603800374 |
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