Increased Circulating Levels of Galectin Proteins in Patients with Breast, Colon, and Lung Cancer

Abstract

Galectins are proteins with high-affinity β-galactoside-binding sites that function in a variety of signaling pathways through interactions with glycoproteins. The known contributions of galectins-1, -3, -7, -8, and -9 to angiogenesis, metastasis, cell division, and evasion of immune destruction led us to investigate the circulating levels of these galectins in cancer patients. This study compares galectin concentrations by enzyme-linked immunosorbent assay (ELISA) from each stage of breast, lung, and colon cancer. Galectins-1 and -7, which share a prototype structure, were found to have statistically significant increases in breast and lung cancer. Of the tandem-repeat galectins, galectin-8 showed no statistically significant change in these cancer types, but galectin-9 was increased in colon and lung cancer. Galectin-3 is the only chimera-type galectin and was increased in all stages of breast, colon, and lung cancer. In conclusion, there were significant differences in the galectin levels in patients with these cancers compared with healthy controls, and galectin levels did not significantly change from stage to stage. These findings suggest that further research on the roles of galectins early in disease pathogenesis may lead to novel indications for galectin inhibitors.

Keywords: ELISA; biorepository; breast; cancer; colon; galectin; lung.

Figure 1

Circulating concentrations of galectins-1, -3, -7, and -9 are increased in breast, colon, and lung cancer patients compared with healthy controls. Cancer galectin levels were determined by ELISA of patient samples. (A,B) Galectins-1 and -3 are increased in all three cancer types, (C) galectin-7 is increased in breast and lung cancer patient samples, (D) galectin-8 shows no statistically significant differences from the healthy control, and (E) galectin-9 is found to be statistically significantly increased in colon and lung cancer. Stars indicate the p-values of nonparametric comparisons with control using the Steel method (* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001). Gal = galectin.

Figure 2

Elevations in circulating levels of galectins-1, -3, -7, and -9 occur in breast, colon, and lung cancer patients compared with healthy controls. Cancer galectin levels were determined by ELISA of patient samples. (A) A statistically significant difference in galectin-1 is shown between stages I and III of breast cancer and healthy controls; (B) galectin-1 is shown to be increased in all stages of colon cancer compared with healthy controls; (C) a statistically significant difference in galectin-1 is shown in stages I, II, and III of lung cancer. (D–F) Galectin-3 is observed to be elevated in all stages of all cancers, (G–I) a statistically significant increase in serum galectin-7 is observed in stage I of breast cancer and stages II and IV of lung cancer, and (J–L) galectin-9 is shown to be increased in stage IV of colon cancer and stages I and IV of lung cancer as compared with healthy controls. Stars indicate the p-values of nonparametric comparisons with control using the Steel method (* p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001). Gal = galectin.

Figure 3

Lung squamous cell carcinoma patients have increased serum levels of galectin-7 relative to lung adenocarcinoma patients. AD is adenocarcinoma. SCC is squamous cell carcinoma. Cancer galectin levels were determined by ELISA of patient serum samples. SCC and healthy control comparison was made using nonparametric comparison with control using the Steel method. SCC and AD comparison was made using the Wilcoxon test (** p ≤ 0.01). Gal = galectin.