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How cancer cells migrate to a secondary site and become established there is not fully understood. An analysis of mouse and human cancer cells could help settle the debate about the role of the protein E-cadherin in this process. Expression of the protein E-cadherin aids the process of metastasis., Author(s): Roger R. Gomis Author Affiliations: Survival skills ensure that cancer spreads When cancer spreads from its primary site to become established at a secondary location, this process, termed metastasis, [...]

Brain metastasis in breast cancer Little is known about the mechanisms by which breast cancer cells metastasize to the brain. Bos et al. now identify three genes that are involved in this process. COX2 and HBEGF have previously been shown to also mediate breast cancer metastasis to the lung, suggesting common biological processes that regulate dissemination to these two organs. In addition, they find that ST6GALNAC5 is specifically involved in brain metastasis, by increasing the adhesion of breast cancer cells to the brain endothelium and migration through the blood-brain barrier. Little is known about the mechanisms by which breast cancer cells metastasize to the brain. By performing gene expression analysis on cells that preferentially infiltrate the brain it has now been possible to identify three genes that are involved in this process, two of which--COX2 and HBEGF--have previously been shown to mediate breast cancer metastasis to the lung. The molecular basis for breast cancer metastasis to the brain is largely unknown.sup.1,2. Brain relapse typically occurs years after the removal of a breast tumour.sup.2,3,4, suggesting that disseminated cancer cells must acquire specialized functions to take over this organ. Here we show that breast cancer metastasis to the brain involves mediators of extravasation through non-fenestrated capillaries, complemented by specific enhancers of blood-brain barrier crossing and brain colonization. We isolated cells that preferentially infiltrate the brain from patients with advanced disease. Gene expression analysis of these cells and of clinical samples, coupled with functional analysis, identified the cyclooxygenase COX2 (also known as PTGS2), the epidermal growth factor receptor (EGFR) ligand HBEGF, and the [alpha]2,6-sialyltransferase ST6GALNAC5 as mediators of cancer cell passage through the blood-brain barrier. EGFR ligands and COX2 were previously linked to breast cancer infiltration of the lungs, but not the bones or liver.sup.5,6, suggesting a sharing of these mediators in cerebral and pulmonary metastases. In contrast, ST6GALNAC5 specifically mediates brain metastasis. Normally restricted to the brain.sup.7, the expression of ST6GALNAC5 in breast cancer cells enhances their adhesion to brain endothelial cells and their passage through the blood-brain barrier. This co-option of a brain sialyltransferase highlights the role of cell-surface glycosylation in organ-specific metastatic interactions., Author(s): Paula D. Bos [sup.1] , Xiang H.-F. Zhang [sup.1] , Cristina Nadal [sup.1] [sup.7] , Weiping Shu [sup.1] , Roger R. Gomis [sup.1] [sup.7] , Don X. Nguyen [sup.1] [...]

Author(s): Gaorav P. Gupta [1, 5]; Don X. Nguyen [1, 5]; Anne C. Chiang [1, 2]; Paula D. Bos [1]; Juliet Y. Kim [1]; Cristina Nadal [1, 6]; Roger R. [...]