Journal
NEOPLASIA
Volume 7, Issue 5, Pages 522-527Publisher
ELSEVIER SCIENCE INC
DOI: 10.1593/neo.04646
Keywords
cancer metastasis; endothelium; adhesion; Thomsen-Friedenreich; antigen; galectins
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Funding
- NCI NIH HHS [R01 CA089827, R01 CA 46120, 1R01CA89827-01, P50 CA069568, R01 CA046120, P50 CA69568, P50 CA103130, P-50 CA103130-01] Funding Source: Medline
- NHLBI NIH HHS [R37 HL-42528-13, T32 HL07094, P01 HL52490-06, T32 HL007094, P01 HL052490] Funding Source: Medline
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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.
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