The Emerging Role of Intelectin-1 in Cancer

Abstract

BackgroundIntelectin (ITLN) is an adipokine with two homologs—ITLN1 and ITLN2—that has various physiological functions. Studies analyzing the relationship between ITLN and cancer are focused on ITLN1; the available literature on ITLN2 and cancer is limited. This review aims to evaluate the role of ITLN1 in cancer without imposing any inclusion criteria, to examine pro- and anticancer roles for ITLN1 and to discuss whether the relationship between ITLN and cancer is mediated by obesity.FindingsOverall, ITLN1 level was highly variable in cancer patients but different from healthy individuals. Compared with control groups, patients with gastrointestinal and prostate cancer showed increased concentrations of circulating ITLN1, while patients with gynecological, breast, bladder, and renal cancer had lower ITLN1 levels. Several studies also evaluated tissue and tumor expression of ITLN1. In gastrointestinal cancer, ITLN1 was increased in tumor tissue compared with adjacent healthy tissue and elevated in the visceral adipose tissue of patients compared with controls. Consequently, the high levels of circulating ITLN1 might be determined by the tumor and by the cancer-associated weight loss in gastrointestinal cancer. ITLN1 can activate the phosphoinositide-3-kinase-protein kinase B/Akt (PI3K/Akt) pathway. The improper regulation of this pathway may contribute to a series of cellular events that favor tumor development and progression. Obesity has been linked with an increased risk of developing some cancers. Indeed, low circulating ITLN1 levels may be a marker of the metabolic effects of obesity, rather than obesity per se, and might contribute to a deregulation of the PI3K/Akt pathway.ConclusionsITLN1 could be associated with cancer formation and progression. Since circulating ITLN1 levels are highly variable and differ between cancer types, the local tumor production of ITLN1 could be more relevant in determining malignant behavior. Future research should aim to identify the source of ITLN1 variability, to understand the differences in ITLN1 between distinct tumor types, and to further explore the signaling pathways through which this adipokine influences cancer biology.

Concentration of Selected Adipokines and Factors Regulating Carbohydrate Metabolism in Patients with Head and Neck Cancer in Respect to Their Body Mass Index

“…Researchers suggested that the concentration of circulating omentin-1 may be a diagnostic marker for breast cancer. Currently, the mechanisms linking omentin-1 to tumor development remain unknown, but studies have indicated that omentin-1 affects the course of cancers with different localizations [ 51 ].…”

A systematic review and Bayesian meta-analysis assessing intelectin-1 in cancer patients and healthy individuals

“…Previous research indicated that circulating ITLN1 concentrations differ between cancer patients and healthy individuals ( 8 – 11 ). Indeed, in our recent narrative review ( 12 ), we observed a difference in circulating ITLN1 levels when people with cancer were compared to healthy individuals. The difference was influenced by cancer type since patients with gastrointestinal and prostate cancer showed higher concentrations of circulating ITLN1, while individuals with breast, bladder, renal and gynaecological cancer expressed lower circulating ITLN1 levels.…”

“…( 20 ) examined the relationship between ITLN1 and cancer in a systematic review and observed that concentrations ranged from 2 to 1100 ng/ml. Whilst comprehensive, their review had some methodological weaknesses that we addressed in a previous study ( 12 ). In healthy people, Watanabe et al.…”

“…Also, obesity was associated with an increased risk of tumour formation ( 17 ) and proposed as a factor that influences the relationship between ITLN1 and cancer ( 18 , 19 ). The decrease of ITLN1 levels observed in overweight and obese individuals could be a marker of the metabolic effects of obesity, contributing to a deregulation of the PI3K/Akt pathway ( 12 ). Therefore, ITLN1 could be a potentially important target in cancer biology.…”

The Role of Selected Adipocytokines in Ovarian Cancer and Endometrial Cancer

“…In ovarian cancer, omentin levels are reduced in patients diagnosed with neoplasia compared to patients with benign gynecological lesions and in healthy women, which may confirm that ovarian cancer cells are capable of downregulating this adipocytokine [ 268 , 271 , 272 ]. Moreover, as indicated by Au-Yeung et al [ 271 ], ovarian cancer cells can suppress ITLN1 expression in mesothelial cells in visceral adipose tissue for cancer cell proliferation and metastasis formation.…”