| | |  | | | | Record from Web of Science® | | | | | | |
| Anoikis and metastatic potential of Cloudman S91 melanoma cells |
|
|
| Author(s): Zhu ZY, Sanchez-Sweatman O, Huang XJ, Wiltrout R, Khokha R, Zhao Q, Gorelik E |
| Source: CANCER RESEARCH Volume: 61 Issue: 4 Pages: 1707-1716 Published: FEB 15 2001 |
| Times Cited: 65 References: 42 |
| Abstract: Anoikis is a form of apoptosis induced in normal cells as a result of loss of their adhesion to substrate. In the present study, we have tested whether tumor cells are also sensitive to anoikis and whether selection of tumor cells for resistance to anoikis could increase their metastatic ability, In vitro cultured Cloudman S91 melanoma cells are strongly adherent to the plastic, Prevention of their adherence by rocking or by covering culture plates with polyhydroxyethylmethacrylate resulted in induction of anoikis and death of almost all cells. Their death was prevented in the presence of caspase inhibitor Z-Val-Ala-Asp-fluoromethyl ketone. To select anoikis-resistant cells, S91 cells floating in the culture medium were sequentially isolated and transferred for seven generations. As a result, a new subline of S91 cells capable of growing in free cell suspension was selected, These S91 nonadherent (S91Nadh) cells were completely resistant to anoikis and manifested higher metastatic ability than S91Adh cells, Anoikis resistance of S91Nadh cells was not attributable to their resistance to other apoptotic signals in vitro, and they showed no increase in their survival in vivo in the lungs after i.v. inoculation. Increased metastatic potential of the anoikis-resistant S91Nadh cells was associated with various phenotypic changes, including increased proliferation and loss of VLA-4 integrin expression because of down-regulation of the VLA-49 alpha (CD49d) gene. In parallel, they showed a reduction in homotypic aggregation and binding to endothelial cells, increased Matrigel invasiveness, and decreased matrix metalloproteinase-2 and matrix metalloproteinase-9 activity that paralleled up-regulation of the TIMP-1 gene. S91Nadh cells also manifested changes in cell surface carbohydrates, such as appearance of alpha -galactosyl epitopes as a result of up-regulation of the alpha1,3-galactosyltransferase gene and concomitant reduction in cell membrane sialylation, Thus, selection of S91 melanoma cells for anoikis resistance resulted in an increase in their metastatic potential in parallel with multiple alterations in their phenotypic properties. |
| Document Type: Article |
| Language: English |
| Reprint Address: Gorelik, E (reprint author), Univ Pittsburgh, Inst Canc, BST,W954, Pittsburgh, PA 15213 USA |
Addresses:
1. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15213 USA
2. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15213 USA
3. Ontario Canc Inst, Toronto, ON M5G 2M9 Canada
4. NCI, Frederick Canc Res & Dev Ctr, Expt Immunol Lab, Expt Therapeut Sect,NIH, Frederick, MD 21702 USA |
| Publisher: AMER ASSOC CANCER RESEARCH, PO BOX 11806, BIRMINGHAM, AL 35202 USA |
| Subject Category: Oncology |
| IDS Number: 407DD |
| ISSN: 0008-5472 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |