Endothelins in Bone Cancer Metastases

Guise, Theresa A.; Mohammad, Khalid S.

doi:10.1007/978-1-4419-9129-4_9

Cited by 51 publications

(19 citation statements)

References 67 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in vascularization observed in the SFC model also included alterations of the vasculature necessary (especially the variation in the number of vessels present near both the bone explant and the tumor mass) for the growth of primary tumors and the formation of metastases [51,52]. Previous studies demonstrate ET-1 modulates angiogenesis and the higher vascularization of breast carcinomas indirectly through the induction of vascular endothelial growth factor (VEGF) [18,49,52].…”

Section: Discussionmentioning

confidence: 94%

Bosentan® inhibits tumor vascularization and bone metastasis in an immunocompetent skin-fold chamber model of breast carcinoma cell metastasis

Dréau

Karaa

Culberson

et al. 2006

Clin Exp Metastasis

View full text Add to dashboard Cite

Angiogenic factors including endothelin-1 (ET-1) play a key role in the progression of breast metastases to bone. We investigated the impact of ET-1 on the development of bone metastases in an immunocompetent murine skin-fold chamber model. Murine mammary carcinoma 4T1 was injected in a skin-fold chamber implanted on CB6 mice along with bone explants. Furthermore, mice were treated with or without a dual selective antagonist of both ET-1 receptors. The progression of the vascularization within the chamber was monitored over time by intravital microscopy (IVM). The tumor growth and the development of bone metastases were assessed by cytokeratin-19 gene expression and histological studies. Results indicate that this new model associated with IVM allows for the continuous monitoring of the change in vascularization associated with the development of bone metastases. Additionally, treatment with an antagonist of both ET-1 receptors was associated with the presence of significantly less vessels near the tumor mass compared to control mice. These changes were correlated with smaller tumor masses and reduced bone invasion (P < 0.05). Thus, in an immunocompetent murine model of breast carcinoma metastases to bone, our data support the hypothesis that vascularization plays a role in tumor development and progression and that ET-1 specifically modulates the angiogenesis associated with breast metastases to the bone.

show abstract

Section: Discussionmentioning

confidence: 94%

Bosentan® inhibits tumor vascularization and bone metastasis in an immunocompetent skin-fold chamber model of breast carcinoma cell metastasis

Dréau

Karaa

Culberson

et al. 2006

Clin Exp Metastasis

View full text Add to dashboard Cite

show abstract

“…c-Src is also known for its pivotal role in enhancing osteoclast activity (Miyazaki et al, 2004;Recchia et al, 2004) and maintaining the osteoblasts in a predifferentiation status (Marzia et al, 2000). These latter cell types are involved in the osteolytic vicious circle in association with the breast cancer cells (Roodman, 2004;Yoneda and Hiraga, 2005) and the endothelial cells that supply angiogenesis and regulatory factors (Guise and Mohammad, 2004;Roodman, 2004;Yoneda and Hiraga, 2005). Therefore, given that all of these cell types could be affected by disruption of c-Src tyrosine kinase activity, we tested whether the pharmacological treatment with an anti-c-Src compound could effectively counteract progression of experimental metastatic disease.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Protein Kinase c-Src Reduces the Incidence of Breast Cancer Metastases and Increases Survival in Mice: Implications for Therapy

Rucci

Recchia

Angelucci

et al. 2006

J Pharmacol Exp Ther

125

102

View full text Add to dashboard Cite

c-Src is a proto-oncogene, belonging to the nonreceptor protein kinases family, which plays a prominent role in carcinogenesis. In this study, we tested the hypothesis that c-Src could promote breast cancer metastasis acting on several cell types and that pharmacological disruption of its kinase activity could be beneficial for the treatment of metastases. Female BALB/cnu/nu mice were subjected to intracardiac injection of the human breast cancer cells MDA-MB-231 (MDA-231), which induced prominent bone and visceral metastases. of a c-Src kinase-dead dominant-negative construct (MDA-231-Src DN ) resulted in reduced morbidity, lethality, and incidence of metastases similar to the mice treated with the inhibitor. An analogous beneficial effect of c-Src inhibition was observed in subcutaneous and intratibial implanted tumors. In vitro, c-Src suppression reduced MDA-231 cell aggressiveness. It also impaired osteoclast bone resorption both directly and by reducing expression by osteoblasts of the osteoclastogenic cytokines interleukin-1␤ and interleukin-6, whereas parathyroid hormone-related peptide was not implicated. c-Src was also modestly but consistently involved in the enhancement of endothelial cell proliferation in vitro and angiogenesis in vivo. In conclusion, we propose that c-Src disruption affects the metastatic process and thus is a therapeutic target for the treatment of breast cancer.Breast cancer is a relatively common tumor, with an estimated incidence of 1.2 million new cases diagnosed worldwide every year (Henderson et al., 1993). The outcome of patients mainly depends on the development of distant metastases (Greenberg et al., 1996). Bone is the principal metastatic site in patients with mammary carcinomas (James et al., 2003), of whom approximately 20% survives for more than 5 years, whereas those with minor metastases in the bone can survive up to 10 years or more. In contrast, visceral metastases, although less common, are more likely to be fatal with a higher risk of early death.Consistent evidence suggests the involvement of the protooncogene c-Src in the development and progression of many human cancers, including breast carcinomas (Otthenoff-Kalff et This work was supported by the E.C. Grant METABRE (LSHM-CT-2003-503049) and by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC).Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

show abstract

“…In preclinical models, administration of an antagonist (ABT-627) to the endothelin-A receptor significantly reduced the osteoblastic response induced by endothelin-1-producing amnion and breast cancer xenografts and reduced the number of metastatic lesions (33,34). Several in vitro and preclinical studies have validated the potentially critical role of the endothelin axis in the tumor-induced osteoblastic response (35,36). In a recent review, Smith and Nelson (37) listed the 13 clinical trials that have been completed or are ongoing with atrasentan (trade name for ABT-627).…”

Section: Strategies To Minimize or Reverse The Osteoblastic Responsementioning

confidence: 99%

Targeting Factors Involved in Bone Remodeling as Treatment Strategies in Prostate Cancer Bone Metastasis

Vessella

Corey

2006

Clinical Cancer Research

View full text Add to dashboard Cite

Prostate cancer is the most commonly diagnosed cancer in men within the western world and the third leading cause of cancer-related deaths. Even if the cancer is considered localized to the prostate, there is a 15% to 20% incidence of subsequent metastatic disease. Prostate cancer has a very high proclivity for metastasizing to bone, with f90% of men with advanced disease having skeletal lesions. The prostate cancer metastases are characteristically osteoblastic, with extensive new bone deposition, unlike other tumors that metastasize to bone and cause an osteolytic response reflective of bone degradation. There are a considerable number of studies relating to inhibition of the osteoblastic response, including interference with endothelin-1, bone morphogenetic proteins, and Wnt signaling pathways.Within the past few years, several studies showed that increased osteolytic activity also occurs in the background of the prostate cancer skeletal metastases. Because growth factors are being released from the bone matrix during degradation, it suggests that inhibition of osteolysis might be effective in slowing tumor growth. Several strategies are being developed and applied to affect directly the osteolytic events, including use of bisphosphonates and targeting the critical biological regulators of osteoclastogenesis, receptor activator of nuclear factor-nB and receptor activator of nuclear factor-nB ligand. This review focuses on several of the clinical and preclinical strategies to inhibit the growth of prostate cancer cells in bone and to alleviate the multitude of associated skeletal-related events.

show abstract

Endothelins in Bone Cancer Metastases

Cited by 51 publications

References 67 publications

Bosentan® inhibits tumor vascularization and bone metastasis in an immunocompetent skin-fold chamber model of breast carcinoma cell metastasis

Bosentan® inhibits tumor vascularization and bone metastasis in an immunocompetent skin-fold chamber model of breast carcinoma cell metastasis

Inhibition of Protein Kinase c-Src Reduces the Incidence of Breast Cancer Metastases and Increases Survival in Mice: Implications for Therapy

Targeting Factors Involved in Bone Remodeling as Treatment Strategies in Prostate Cancer Bone Metastasis

Contact Info

Product

Resources

About