Galectin-1, -3 and -9 Expression and Clinical Significance in Squamous Cervical Cancer

Abstract

Galectins are proteins that bind β-galactoside sugars and provide a new type of potential biomarkers and therapeutic targets in cancer. Galectin-1, -3 and -9 have become the focus of different research groups, but their expression and function in cervical cancer is still unclear. The aim of this study was to determine the phenotype of galectin-1, -3 and -9 expressing cells and the association with clinico-pathological parameters in cervical cancer. Galectin expression was scored in tumor cells, tumor epithelium infiltrating immune cells and stromal cells in squamous cervical cancer (n = 160). Correlations with clinico-pathological parameters and survival were studied according to the REMARK recommendations. We additionally investigated whether the galectins were expressed by tumor cells, fibroblasts, macrophages and T cells. Galectin-1 and -9 were both expressed by tumor cells in 11% of samples, while 84% expressed galectin-3. Strong galectin-1 expression by tumor cells was an independent predictor for poor survival (hazard ratio: 8.02, p = 0.001) and correlated with increased tumor invasion (p = 0.032) and receiving post-operative radiotherapy (p = 0.020). Weak and positive tumor cell galectin-3 expression were correlated with increased and decreased tumor invasion, respectively (p = 0.012). Tumor cell expression of galectin-9 showed a trend toward improved survival (p = 0.087). The predominant immune cell type expressing galectin-1, -3 and -9 were CD163+ macrophages. Galectin-1 and -3 were expressed by a minor population of T cells. Galectin-1 was mainly expressed by fibroblasts in the tumor stroma. To conclude, while tumor cell expression of galectin-9 seemed to represent a beneficial response, galectin-1 expression might be used as a marker for a more aggressive anti-cancer treatment.

Exploring the Structural Space of the Galectin‐1–Ligand Interaction

“…It has been associated with tumor proliferation, angiogenesis, and metastasis . Galectin‐1‐secreting tumors gain immune privilege by inducing apoptosis in T‐helper cells, and its expression level correlates with the aggressiveness of certain tumors . Many of these processes are mediated by the sophisticated interplay between the lectin and the β‐galactosides of complex glycan structures presented on the cell surface.…”

A key role for galectin‐1 in sprouting angiogenesis revealed by novel rationally designed antibodies

“…Apart from possible applications in nuclear imaging, we also evaluated the use of the antibodies in immunohistochemical analyses. Immunohistological stainings on tissues can reveal the (sub)cellular distribution of galectin‐1, which has been shown to be of added value for galectins . For example, elevated galectin‐1 expression in malignant tissues is frequently confined to the stromal compartment.…”

“…Moreover, deregulated expression or function of galectin‐1 is frequently associated with disease, most notably with inflammatory disorders and cancer . Regarding the latter, we and others have shown that increased galectin‐1 expression is associated with poor survival in many cancer types . This has been attributed to the capacity of galectin‐1 to suppress the anti‐tumor immune response, to induce tumor angiogenesis, and to promote tumor metastasis .…”

“…10,11 Regarding the latter, we and others have shown that increased galectin-1 expression is associated with poor survival in many cancer types. [11][12][13] This has been attributed to the capacity of galectin-1 to suppress the anti-tumor immune response, 14,15 to induce tumor angiogenesis, 16,17 and to promote tumor metastasis. 18,19 Given these tumor-promoting activities, galectin-1 is considered a potential target for cancer therapy.…”

Inside Cover: Exploring the Structural Space of the Galectin‐1–Ligand Interaction (ChemBioChem 15/2017)

“…[2] Galectin-1-secreting tumors gain immune privilegeb y inducing apoptosis in T-helperc ells, [3] andi ts expression level correlates with the aggressiveness of certain tumors. [4] Many of these processes are mediated by the sophisticated interplay between the lectin and the b-galactosides of complex glycan structures presented on the cell surface. Owing to the overexpression of galectin-1 in numerous types of cancerc ell lines, the protein has been suggested as ap otential target for therapeutic intervention [5] and ad iagnostic marker.…”