Lipocalin-2 is associated with radioresistance in oral cancer and lung cancer cells

Abstract

The aim of the present study was to identify a target molecule that could predict the efficacy of radiotherapy in oral squamous cell carcinoma (OSCC). We used DNA microarray analysis to identify differences in gene expression after X-ray irradiation. We compared the gene expression profiles between X-ray (8 Gy)-irradiated Ca9-22 cells (an OSCC-derived cell line) and unirradiated Ca9-22 cells. A total of 167 genes with a 2-fold higher level of expression induced by X-ray irradiation were identified. Lipocalin-2 (LCN2) had the greatest increase in expression after X-ray irradiation, and it was categorized in a network that has cancer-related functions with the Ingenuity Pathway Analysis tool. Upregulated expression of LCN2 mRNA was validated by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. When the LCN2 gene was knocked down in OSCC cells (Ca9-22 and HSC-2) and lung cancer cells (A549) by using small interfering RNA, the radiosensitivity of these cells was enhanced. Our findings suggest that the overexpression of LCN2 is likely associated with radioresistance in oral cancer and lung cancer cells, and that LCN2 expression levels could be used to predict radioresistance. Thus, regulating the expression or function of LCN2 could enhance the radiation response, resulting in a favorable outcome of radiotherapy.

Gprc5a-knockout mouse lung epithelial cells predicts ceruloplasmin, lipocalin 2 and periostin as potential biomarkers at early stages of lung tumorigenesis

“…Lipocalin 2 has been identified as a stress protein that is released in a variety of other sterile inflammatory conditions such as adipose obesity-related inflammation [20] and cancer. Recently, it has been reported that Lipocalin 2 is associated with radioresistance in oral cancer and lung cancer cells [21], and erlotinib resistance in NSCLC [22]. Functionally, Lipocalin 2 has been suggested in promoting tumorigenesis through enhancing tumor cell survival and proliferation, and metastatic potential [23–25].…”

Roles of NGAL and MMP-9 in the tumor microenvironment and sensitivity to targeted therapy

“…Many transcription factors, including the estrogen and androgen receptors, regulate NGAL expression by both positive and negative mechanisms [67][68][69][70][71][72][73][74][75][76][77]. 11 NGAL is an important molecule in many different types of cancer including: breast [9,10,77], colorectal (CRC) [78,79], endometrial [80], esophageal [7,81], gastric cancer [6], liver [82][83][84], lung [85][86][87] ovarian [88], pancreatic [89,90], prostate [76,91], renal [8,92] and thyroid cancer [68]. In general, elevated NGAL expression has been associated with advanced cancer and poor prognosis.…”

“…When expression of NGAL was knocked down with small interfering RNA (siRNA), the sensitivity of the oral cancer Ca9-22 and HSC-2 cells to radiation was increased. The authors have suggested that NGAL expression may be used to predict radioresistance[85].The expression of NGAL was detected in 58/78 (76.3%) lung cancers and 4/30 (13.3%) adjacent tissues indicating that NGAL expression was more present in cancerous than non-cancerous adjacent tissues. The mechanisms of invasion in A549 lung cancer cells and the role of NGAL expression were examined.…”

Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities

“…Lipocalin-2 (LCN2), which is a member of the lipocalin family and functions to ligate ferric siderophore-like molecules, is involved in various cancers including lung cancer (Shiiba et al, 2013 ), breast cancer (Yang et al, 2013 ), ovarian cancer (Cho and Kim, 2009 ), colon cancer and pancreatic cancer (Mannelqvist et al, 2012 ). The elevated levels of LCN2 tightly associate with the malignance and metastasis of cancer cells (Leng et al, 2009 ; Yang et al, 2009 ).…”