Lipocalin 2 performs contrasting, location-dependent roles in APCmin tumor initiation and progression

Reilly, Patrick T.; Teo, Wei; Low, Meijun; Amoyo-Brion, A A; Dominguez-Brauer, Carmen; Elia, Andrew; Berger, Thorsten; Greicius, Gediminas; Pettersson, Sven; Mak, Tak W.

doi:10.1038/onc.2012.159

Cited by 20 publications

(15 citation statements)

References 48 publications

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“…Tnfsf10 , which is involved in the tumor necrosis factor-related apoptosis-induced ligand (TRAIL) apoptotic pathway, is dysregulated in both Apc Min/+ tumors and human polyps (34–36). Elevated lipocalin 2, a molecule involved in innate immunity and iron metabolism (37), has been found in both Apc Min/+ tumors and human CRC (38,39) and may function as either a tumor suppressor or promoter depending on location in the intestine (40). All of these results need to be confirmed in larger samples and by quantitative PCR before definitive statements can be made about their role in tumor formation and progression in this model.…”

Section: Discussionmentioning

confidence: 99%

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Olson

Hadac

Sievers

et al. 2014

Cancer Prevention Research

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Colorectal cancer (CRC) often arises from adenomatous colonic polyps. Polyps can grow and progress to cancer, but may also remain static in size, regress, or resolve. Predicting which progress and which remain benign is difficult. We developed a novel long-lived murine model of CRC with tumors that can be followed by colonoscopy. Our aim was to assess whether these tumors have similar growth patterns and histologic fates to human colorectal polyps to identify features to aid in risk-stratification of colonic tumors. Long-lived ApcMin/+ mice were treated with dextran sodium sulfate to promote colonic tumorigenesis. Tumor growth patterns were characterized by serial colonoscopy with biopsies obtained for immunohistochemistry and gene expression profiling. Tumors grew, remained static, regressed, or resolved over time with different relative frequencies. Newly developed tumors demonstrated higher rates of growth and resolution than more established tumors that tended to remain static in size. Colonic tumors were hyperplastic lesions (3%), adenomas (73%), intramucosal carcinomas (20%), or adenocarcinomas (3%). Interestingly, the level of β-catenin was higher in adenomas that became intratumoral carcinomas as compared to those that failed to progress. In addition, differentially expressed genes between adenomas and intramucosal carcinomas were identified. This novel murine model of intestinal tumorigenesis develops colonic tumors that can be monitored by serial colonoscopy, mirror growth patterns seen in human colorectal polyps, and progress to CRC. Further characterization of cellular and molecular features are needed to determine which features can be used to risk-stratify polyps for progression to CRC and potentially guide prevention strategies.

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Section: Discussionmentioning

confidence: 99%

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Olson

Hadac

Sievers

et al. 2014

Cancer Prevention Research

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“…NGAL is considered by some scientists to have properties of an oncogene, or in some cases, a tumor suppressor gene [9,10,73,89,96,[127][128][129][130][131][132][133][134]. Increased levels of NGAL have been detected in the urine and plasma of patients with various types of cancer (i.e.…”

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confidence: 99%

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

Candido

Abrams

Steelman

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Various, diverse molecules contribute to the tumor microenvironment and influence invasion and metastasis. In this review, the roles of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9) in the tumor microenvironment and sensitivity to therapy will be discussed. The lipocalin family of proteins has many important functions. For example when NGAL forms a complex with MMP-9 it increases its stability which is important in cancer metastasis. Small hydrophobic molecules are bound by NGAL which can alter their entry into and efflux from cells. Iron transport and storage are also influenced by NGAL activity. Regulation of iron levels is important for survival in the tumor microenvironment as well as metastasis. Innate immunity is also regulated by NGAL as it can have bacteriostatic properties. NGAL and MMP-9 expression may also affect the sensitivity of cancer cells to chemotherapy as well as targeted therapy. Thus NGAL and MMP-9 play important roles in key processes involved in metastasis as well as response to therapy. This article is part of a Special Issue entitled: Tumor Microenvironment Regulation of Cancer Cell Survival, Metastasis, Inflammation, and Immune Surveillance edited by Peter Ruvolo and Gregg L. Semenza.

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“…Cocaging of these mice from the time of weaning ensured that mice were exposed to the same physical and microbial environment. The phenotype was examined when one animal of each pair reached a humane endpoint as this provides maximum allowable phenotypic presentation (14).…”

Section: Resultsmentioning

confidence: 99%

“…In this context, our finding of a colon-specific effect of an inflammation gene is not surprising. Indeed, it is somewhat surprising that other inflammation pathways do not manifest a similar colon-specific effect (10,11,14,21).…”

Section: Discussionmentioning

confidence: 99%

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CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model

Leo

Tan

Bergmann

et al. 2015

Cancer Immunology Research

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Caspase recuitment domain-containing protein 9 (CARD9) functions in different inflammation pathways to elicit responses to microbial signals and is known to affect intestinal inflammation. Examining the APC min mouse model of intestinal tumorigenesis and using stringently controlled, sex-and age-matched pairs of CARD9-competent and CARD9-deficient mice, we have found that CARD9 has a restricted but strong effect on tumorigenesis in the large intestine. We have found that CARD9 reduces viability specifically in males and promotes tumorigenesis specifically in the large intestines of these male mice. To our knowledge, this is the first gene ablation in APC min mice that solely affects colon tumors in male subjects and, as such, may have significant clinical implications. Additional data suggest correlative disruption of plasma cytokine expression and immune infiltration of the tumors. We speculate that known sex-specific differences in human colorectal cancer may involve inflammation, particularly CARD9-dependent inflammation. Cancer Immunol Res; 3(7); 721-6. Ó2015 AACR.

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Lipocalin 2 performs contrasting, location-dependent roles in APCmin tumor initiation and progression

Cited by 20 publications

References 48 publications

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

Dynamic Tumor Growth Patterns in a Novel Murine Model of Colorectal Cancer

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

CARD9 Promotes Sex-Biased Colon Tumors in the APCmin Mouse Model

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