Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone

Abstract

Introduction Studies in xenograft models and experimental models of metastasis have implicated several β3 integrinexpressing cell populations, including endothelium, platelets and osteoclasts, in breast tumor progression. Since orthotopic human xenograft models of breast cancer are poorly metastatic to bone and experimental models bypass the formation of a primary tumor, however, the precise contribution of tumorspecific αvβ3 to the spontaneous metastasis of breast tumors from the mammary gland to bone remains unclear.

Reduced tumour cell proliferation and delayed development of high-grade mammary carcinomas in cathepsin B-deficient mice

“…Cathepsin X is unique among the cysteine cathepsins in containing an RGD peptide that mediates binding to a v b 3 integrin (Lechner et al, 2006). Strikingly, the extracellular portion of a v b 3 integrin has been shown to promote adhesion and bone metastasis of mammary epithelial cells, while the cytoplasmic b 3 enhances the tumourigenic proliferation and growth of oncogene-transformed cancer cells (Sloan et al, 2006;Huveneers et al, 2007). Hence, redistribution of cathepsin X is likely to explain the relatively high level of metastasis and proliferation of Ctsb-deficient PyMT cells compared to PyMT;Ctsb þ /À cells (Vasiljeva et al, 2006) (Figure 4; Table 1).…”

Molecular discrimination of cutaneous squamous cell carcinoma from actinic keratosis and normal skin

“…[40][41][42] Lymph node and bone metastases have been associated with specific integrins in melanoma, breast carcinoma, prostate carcinoma, and pancreatic carcinoma. [43][44][45][46][47] The use of integrin antagonists in glioblastoma and colorectal carcinoma as a therapeutic modality has shown promise in clinical trials. 48,49 The finding of deregulated integrin signaling in our study is not surprising as the upregulation of different integrins has been previously demonstrated in cutaneous squamous cell carcinomas.…”

In vitro assessment of the dual-targeting behavior of a peptide-based magnetic resonance imaging contrast agent

“…In tumor cells expressing both α v β 3 and CD 13 , the two motifs of RGD and NGR can simultaneously bind to the target tissue, which enhances the incorporation of the contrast agent; the higher concentration of the contrast agent in the tumor area will improve imaging visibility. In this study, the targeting behavior of the contrast agent that we designed was examined using MDA-MB-231 human breast cancer cells (which overexpress α v β 3 ) (19,20) and PC-3 human prostate cancer cells (which overexpress CD 13 ) (21). 4,7,10- 3 ].…”