Inhibition of tumor formation by snake venom disintegrin
Journal
Toxicon
Journal Volume
45
Journal Issue
5
Pages
661-669
Date Issued
2005
Author(s)
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in nude mice, histological examination of the tibia of control group revealed that most of the cancellous bone had been replaced by the breast cancer cells after 28 days' inoculation.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. ? 2005 Elsevier Ltd. All rights reserved.
SDGs
Other Subjects
abciximab; alpha2 integrin; alpha3 integrin; alpha5 integrin; beta1 integrin; disintegrin; paclitaxel; protein subunit; rhodostomin; snake venom; triflavin; trigramin; unclassified drug; vitronectin receptor; animal cell; animal experiment; animal model; animal tissue; antibody specificity; antigen binding; article; bone destruction; bone metastasis; bone mineralization; breast carcinoma; cancellous bone; cancer chemotherapy; cancer inhibition; carcinogenesis; carcinoma cell; cell adhesion; cell invasion; cell migration; cell viability; controlled study; examination; extracellular matrix; fetus; histology; human; human cell; injection; inoculation; molecular recognition; mouse; nonhuman; nude mouse; priority journal; prostate carcinoma; rat; tibia; Mus musculus; Serpentes
Type
journal article