Localization of endogenous lectins in normal human breast, benign breast lesions and mammary carcinomas

Gabius, Hans‐Joachim; Schauer, A.; Cramer, Friedrich

doi:10.1007/bf02889955

Cited by 83 publications

(45 citation statements)

References 17 publications

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“…33). Elevated stromal expression of gal-1 has been reported in several cancers, including cancer of the ovaries (35), breast (36), prostate (37), and colon (38). These results suggest that the increased expression in tumors makes the protein an excellent target for diagnostic or therapeutic purposes.…”

Section: Discussionmentioning

confidence: 94%

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Thijssen¹,

Postel

Brandwijk³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

433

406

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We describe that galectin-1 (gal-1) is a receptor for the angiogenesis inhibitor anginex, and that the protein is crucial for tumor angiogenesis. gal-1 is overexpressed in endothelial cells of different human tumors. Expression knockdown in cultured endothelial cells inhibits cell proliferation and migration. The importance of gal-1 in angiogenesis is illustrated in the zebrafish model, where expression knockdown results in impaired vascular guidance and growth of dysfunctional vessels. The role of gal-1 in tumor angiogenesis is demonstrated in gal-1-null mice, in which tumor growth is markedly impaired because of insufficient tumor angiogenesis. Furthermore, tumor growth in gal-1-null mice no longer responds to antiangiogenesis treatment by anginex. Thus, gal-1 regulates tumor angiogenesis and is a target for angiostatic cancer therapy.angiostatic therapy ͉ endothelial cell ͉ galectin ͉ tumor models ͉ anginex A n adequate vasculature is a prerequisite for tumors to grow, and the need for neovessel formation (or angiogenesis) provides a target for treatment of cancer (1). Endothelial cells (EC) that line the tumor vasculature are particularly suitable target cells for therapeutic approaches, because they are easily accessible to agents delivered by the blood (2). However, to affect only tumor vasculature, specific targets on angiogenically active EC are essential. To date, only a few targets of tumor vasculature have been identified (3).We recently developed the specific angiostatic peptide anginex, which inhibits tumor growth through specific inhibition of angiogenesis (4-6). Although a broad profile of activities of anginex is known, such as prevention of EC adhesion and induction of apoptosis, the molecular target on tumor EC was never identified. In a receptor-finding study using a yeast twohybrid screening approach, we identified galectin-1 (gal-1) as a target protein of anginex.gal-1 belongs to a family of carbohydrate-binding proteins that share a conserved carbohydrate recognition domain of Ϸ130 aa (7-9). Over a dozen mammalian galectins have been described (10, 11), and members of this family are expressed in a wide range of species, suggesting an important role for galectins in basic cellular mechanisms. Galectins can be secreted and, depending on the cell type or state of differentiation, they have been found in the nucleus, cytoplasm, or extracellular matrix. It has been proposed that gal-1 mediates cell adhesion and migration (12) and is involved in several processes, including proliferation (13), apoptosis (14), and even mRNA splicing (15). The role of gal-1 in EC function or vascular biology has not been extensively studied.Here, we describe the function of gal-1 in angiogenesis. We provide direct functional evidence that gal-1 is required for tumor angiogenesis and outgrowth of tumors. Furthermore, we show that gal-1 is the target for the potent angiogenesis inhibitor anginex, thus establishing gal-1 as an important target for anticancer therapy.Results gal-1 Binds the Angiostatic Peptide Anginex...

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Section: Discussionmentioning

confidence: 94%

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Thijssen¹,

Postel

Brandwijk³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

433

406

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show abstract

“…Gal-1 binds β-galactoside groups on various cell surface receptors, is highly upregulated in tumor-activated endothelial cells, and is crucial for activated endothelial cells to adhere to, and to migrate on, the extracellular matrix [9,[13][14][15]. Differential stromal elevation of gal-1 over the tumor parenchyma has been reported in several cancers including cancer of the breast [16], colon [17], prostate [18,19] and ovaries [20]. On the molecular level, interaction between anginex and galectin-1 inhibits tumor-activated endothelial cell proliferation via anoikis [21] and attenuates tumor angiogenesis and tumor growth [22][23][24].…”

Section: Introductionmentioning

confidence: 99%

Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven

Dings

Laar²,

Webber³

et al. 2008

Cancer Letters

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Combination of chemotherapeutic agents and angiogenesis inhibitors is now commonly employed in the clinic to treat cancer. Here, we used angiostatic agents anginex and 0118, in combination with the chemotherapeutic irofulven, to treat human ovarian tumor xenografts in mice. General linear mixed models were used to statistically analyze tumor growth curves. Overall, combination of a low, non-toxic dose of irofulven with either angiogenesis inhibitor was more effective at inhibiting tumor growth than any of the single-agent therapies. For example, the anginex/irofulven and 0118/irofulven combinations inhibited tumor growth relative to controls by 92% (p<0.0001) and 96% (p<0.0001), respectively, with the 0118/irofulven combinations yielding 100% complete responses. This study suggests that combination therapy of 0118 or anginex and irofulven may be highly effective in the clinical setting.

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“…20 This reasoning has prompted the monitoring of galectins in malignant human tumor specimens, such as sections from breast, thyroid, and brain carcinoma, and also the initial demonstration of the presence of galectin in HNSCC cell lines and 35 primary HNSCCs. [21][22][23][24] However, no study so far has applied biochemically purified galectins simultaneously to determine the extent of lectin-reactive sites and galectin specific antibodies.…”

mentioning

confidence: 99%

The levels of expression of galectin-1, galectin-3, and the Thomsen-Friedenreich antigen and their binding sites decrease as clinical aggressiveness increases in head and neck cancers

Choufani

Nagy

Saussez

et al. 1999

Cancer

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Localization of endogenous lectins in normal human breast, benign breast lesions and mammary carcinomas

Cited by 83 publications

References 17 publications

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Galectin-1 is essential in tumor angiogenesis and is a target for antiangiogenesis therapy

Ovarian tumor growth regression using a combination of vascular targeting agents anginex or topomimetic 0118 and the chemotherapeutic irofulven

The levels of expression of galectin-1, galectin-3, and the Thomsen-Friedenreich antigen and their binding sites decrease as clinical aggressiveness increases in head and neck cancers

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