Endoglin suppresses human prostate cancer metastasis.
Summary of "Endoglin suppresses human prostate cancer metastasis."
Endoglin is a transmembrane receptor that suppresses human prostate cancer (PCa) cell invasion. Small molecule therapeutics now being tested in humans can activate endoglin signaling. It is not known whether endoglin can regulate metastatic behavior, PCa tumor growth, nor what signaling pathways are linked to these processes. This study sought to investigate the effect of endoglin on these parameters. We used a murine orthotopic model of human PCa metastasis, designed by us to measure effects at early steps in the metastatic cascade, and implanted PCa cells stably engineered to express differing levels of endoglin. We now extend this model to measure cancer cells circulating in the blood. Progressive endoglin loss led to progressive increases in the number of circulating PCa cells as well as to the formation of soft tissue metastases. Endoglin was known to suppress invasion by activating the Smad1 transcription factor. We now show that it selectively activates specific Smad1-responsive genes, including JUNB, STAT1, and SOX4. Increased tumor growth and increased Ki67 expression in tissue was seen only with complete endoglin loss. By showing that endoglin increased TGFβ-mediated suppression of cell growth in vitro and TGFβ-mediated signaling in tumor tissue, loss of this growth-suppressive pathway appears to be implicated at least in part for the increased size of endoglin-deficient tumors. Endoglin is shown for the first time to suppress cell movement out of primary tumor as well as the formation of distant metastasis. It is also shown to co-regulate tumor growth and metastatic behavior in human PCa.
Affiliation
Department of Medicine, Northwestern University Medical School, Lurie 6-105, 303 E. Superior Street, Chicago, IL, 60611, USA.
Journal Details
This article was published in the following journal.
Name: Clinical & experimental metastasis
ISSN: 1573-7276
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20981476
- DOI: http://dx.doi.org/10.1007/s10585-010-9356-6
Medical and Biotech [MESH] Definitions
Prostate-specific Antigen
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
Prostatic Secretory Proteins
Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.
Fenretinide
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Ultrasound, High-intensity Focused, Transrectal
Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).
Inflammatory Breast Neoplasms
Metastatic breast cancer characterized by EDEMA and ERYTHEMA of the affected breast due to LYMPHATIC METASTASIS and eventual obstruction of LYMPHATIC VESSELS by the cancer cells.
PubMed Articles
Information on the impact of bone metastasis and skeletal-related events (SREs) on mortality among prostate cancer patients is limited. Using the linked Surveillance, Epidemiology and End Results (SEE...
OBJECTIVE: To determine the relation between concentrations of prostate specific antigen at age 60 and subsequent diagnosis of clinically relevant prostate cancer in an unscreened population to evalua...
UCH-L1 promotes cancer metastasis in prostate cancer cells through EMT induction.
Ubiquitin C-terminal hydrolse-L1 (UCH-L1) is a deubiquitinating enzyme (DUB) that cleaves the ubiquitin (ub) moiety from ub precursors or protein substrates. The correlation between UCH-L1 and cancer...
Thyroid hormone suppresses cell proliferation through endoglin-mediated promotion of p21 stability.
Hypothyroidism has been associated with significantly elevated risk for hepatocellular carcinoma (HCC), although the precise underlying mechanisms remain unknown at present. Thyroid hormone (T(3)) and...
More than 15 years ago, the first generation of genetically engineered mouse (GEM) models of prostate cancer was introduced. These transgenic models utilized prostate-specific promoters to express SV...
Clinical Trials
Study to determine effectiveness and safety of zoledronic acid and whether it has a pharmaco-economic impact in prostate cancer with bone metastasis.
Bisphosphonates have been used extensively in the treatment and the prevention of skeletal complications associated with bone metastases in patients with breast cancer and prostate cancer....
Effect of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastasis
It is the aim of this clinical study to evaluate the skeletal-related event rate and tolerability of zoledronic acid in patients with prostate cancer patients and bone metastases.
Studies of Hereditary Hemorrhagic Telangiectasia
OBJECTIVES: I. Examine screening modalities for pulmonary vascular arteriovenous malformation (PAVM) in individuals with endoglin mutations. II. Examine the prevalence of cerebral arter...
The study aims to evaluate if adding vertebroplasty to radiotherapy, in the treatment of spine metastasis from breast and prostate cancer, is preferable to radiotherapy alone. The investi...
