Abstract
The metastasis of tumor cells to bone involves migration, invasion and adhesion to bone. Breast and prostate cancer cells have predilection for spreading to bone. Snake venom-derived arginine-glycine-aspartic acid (RGD)-containing disintegrins (e.g. rhodostomin) have been demonstrated to inhibit cell adhesion. Here, we found that rhodostomin inhibited the adhesion of breast and prostate carcinoma cells to both unmineralized and mineralized bone extracellular matrices in a dose-dependent manner, without affecting the viability of tumor cells. In addition, rhodostomin also inhibited the migration and invasion of breast and prostate carcinoma cells. It specifically inhibited the binding of monoclonal antibody (MoAb) 7E3, which recognizes integrin αvβ3, to tumor cells, but not those of other MoAbs against other integrin subunits such as α2, α3, α5 and β1. As breast cancer cells MDA-MB-231 were locally injected into tibia in nude mice, histological examination of the tibia of control group revealed that most of the cancellous bone had been replaced by the breast cancer cells after 28 days' inoculation. In contrast, co-administration of trigramin with cancer cells markedly inhibited tumor growth and bone destruction. Taken together, disintegrins strongly inhibit the adhesion, migration, invasion of tumor cells and also tumor growth of human breast cancer cells in bone as well. Therefore, disintegrins may be developed as alternate therapy for bone metastasis of cancer cells.
| Original language | English |
|---|---|
| Pages (from-to) | 661-669 |
| Number of pages | 9 |
| Journal | Toxicon |
| Volume | 45 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - 2005 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Toxicology
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Inhibition of tumor formation by snake venom disintegrin. / Yang, Rong Sen; Tang, Chih Hsin; Chuang, Woei-Jer; Huang, Tsang-Hai; Peng, Hui Chin; Huang, Tur Fu; Fu, Wen Mei.
In: Toxicon, Vol. 45, No. 5, 01.01.2005, p. 661-669.Research output: Contribution to journal › Article
TY - JOUR
T1 - Inhibition of tumor formation by snake venom disintegrin
AU - Yang, Rong Sen
AU - Tang, Chih Hsin
AU - Chuang, Woei-Jer
AU - Huang, Tsang-Hai
AU - Peng, Hui Chin
AU - Huang, Tur Fu
AU - Fu, Wen Mei
PY - 2005/1/1
Y1 - 2005/1/1
N2 - The metastasis of tumor cells to bone involves migration, invasion and adhesion to bone. Breast and prostate cancer cells have predilection for spreading to bone. Snake venom-derived arginine-glycine-aspartic acid (RGD)-containing disintegrins (e.g. rhodostomin) have been demonstrated to inhibit cell adhesion. Here, we found that rhodostomin inhibited the adhesion of breast and prostate carcinoma cells to both unmineralized and mineralized bone extracellular matrices in a dose-dependent manner, without affecting the viability of tumor cells. In addition, rhodostomin also inhibited the migration and invasion of breast and prostate carcinoma cells. It specifically inhibited the binding of monoclonal antibody (MoAb) 7E3, which recognizes integrin αvβ3, to tumor cells, but not those of other MoAbs against other integrin subunits such as α2, α3, α5 and β1. As breast cancer cells MDA-MB-231 were locally injected into tibia in nude mice, histological examination of the tibia of control group revealed that most of the cancellous bone had been replaced by the breast cancer cells after 28 days' inoculation. In contrast, co-administration of trigramin with cancer cells markedly inhibited tumor growth and bone destruction. Taken together, disintegrins strongly inhibit the adhesion, migration, invasion of tumor cells and also tumor growth of human breast cancer cells in bone as well. Therefore, disintegrins may be developed as alternate therapy for bone metastasis of cancer cells.
AB - The metastasis of tumor cells to bone involves migration, invasion and adhesion to bone. Breast and prostate cancer cells have predilection for spreading to bone. Snake venom-derived arginine-glycine-aspartic acid (RGD)-containing disintegrins (e.g. rhodostomin) have been demonstrated to inhibit cell adhesion. Here, we found that rhodostomin inhibited the adhesion of breast and prostate carcinoma cells to both unmineralized and mineralized bone extracellular matrices in a dose-dependent manner, without affecting the viability of tumor cells. In addition, rhodostomin also inhibited the migration and invasion of breast and prostate carcinoma cells. It specifically inhibited the binding of monoclonal antibody (MoAb) 7E3, which recognizes integrin αvβ3, to tumor cells, but not those of other MoAbs against other integrin subunits such as α2, α3, α5 and β1. As breast cancer cells MDA-MB-231 were locally injected into tibia in nude mice, histological examination of the tibia of control group revealed that most of the cancellous bone had been replaced by the breast cancer cells after 28 days' inoculation. In contrast, co-administration of trigramin with cancer cells markedly inhibited tumor growth and bone destruction. Taken together, disintegrins strongly inhibit the adhesion, migration, invasion of tumor cells and also tumor growth of human breast cancer cells in bone as well. Therefore, disintegrins may be developed as alternate therapy for bone metastasis of cancer cells.
UR - http://www.scopus.com/inward/record.url?scp=15044341611&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=15044341611&partnerID=8YFLogxK
U2 - 10.1016/j.toxicon.2005.01.013
DO - 10.1016/j.toxicon.2005.01.013
M3 - Article
VL - 45
SP - 661
EP - 669
JO - Toxicon
JF - Toxicon
SN - 0041-0101
IS - 5
ER -