Mechanical entrapment is insufficient and intercellular adhesion is essential for metastatic cell arrest in distant organs.
نویسندگان
چکیده
In this report, we challenge a common perception that tumor embolism is a size-limited event of mechanical arrest, occurring in the first capillary bed encountered by blood-borne metastatic cells. We tested the hypothesis that mechanical entrapment alone, in the absence of tumor cell adhesion to blood vessel walls, is not sufficient for metastatic cell arrest in target organ microvasculature. The in vivo metastatic deposit formation assay was used to assess the number and location of fluorescently labeled tumor cells lodged in selected organs and tissues following intravenous inoculation. We report that a significant fraction of breast and prostate cancer cells escapes arrest in a lung capillary bed and lodges successfully in other organs and tissues. Monoclonal antibodies and carbohydrate-based compounds (anti-Thomsen-Friedenreich antigen antibody, anti-galectin-3 antibody, modified citrus pectin, and lactulosyl-l-leucine), targeting specifically beta-galactoside-mediated tumor-endothelial cell adhesive interactions, inhibited by >90% the in vivo formation of breast and prostate carcinoma metastatic deposits in mouse lung and bones. Our results indicate that metastatic cell arrest in target organ microvessels is not a consequence of mechanical trapping, but is supported predominantly by intercellular adhesive interactions mediated by cancer-associated Thomsen-Friedenreich glycoantigen and beta-galactoside-binding lectin galectin-3. Efficient blocking of beta-galactoside-mediated adhesion precludes malignant cell lodging in target organs.
منابع مشابه
Gene Expression Changes in Pomegranate Peel Extract-Treated Triple-Negative Breast Cancer Cells
Background: Triple-negative breast cancer (TNBC) is treated with highly aggressive non-targeted chemotherapies. Safer and more effective therapeutic approaches than those currently in use are needed. Natural pomegranate peel extract (PPE) has recently been found to inhibit breast cancer progression; however, its mechanisms of action remain unclear. We hypothesized that transcriptional chan...
متن کاملEffect of one Bout Continuous Versus Intermittent Aerobic Exercise on Plasma Levels of Intercellular Adhesion Molecules 1 and Vascular Cell Adhesion Molecules 1 in Patients with Coronary Heart Disease
Introduction: Adhesion molecules play an important role in the pathogenesis of atherosclerosis and the type of training may affect the response to these indicators. Therefore, the purpose of the present study was to investigate the effect of a continuous versus interval aerobic training session on plasma levels of intercellular adhesion molecules 1 (ICAM-1) and vascular cell adhesion molecules ...
متن کاملTissue-specific Microvascular Endothelial Cell Lines from H-2K-tsA58 Mice for Studies of Angiogenesis and Metastasis
Microvascular endothelial cells play a critical role in tumor progression and metastasis by forming capillary networks that encourage tumor growth and by promoting the attachment of circulating tumor cells to the vascular wall of distant tissues. Efforts to study the molecular mechanisms that mediate these complex processes in different anatomical compartments have been impeded by difficulties ...
متن کاملHistopathological expression analysis of intercellular adhesion molecule 1 (ICAM-1) along development and progression of human melanoma
Intercellular adhesion molecule 1 (ICAM-1) protein is an important adhesion molecule that facilitates metastasis on one hand, and on the other hand supports the immunological synapse necessary for T-cell mediated elimination. The expression pattern of ICAM-1 in melanoma was studied more than two decades ago, mainly in cell lines or in unmatched melanoma specimens. By using real time PCR we coul...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Neoplasia
دوره 7 5 شماره
صفحات -
تاریخ انتشار 2005