Macrophage-derived IL-1beta Stimulates Wnt Signaling and Growth of Colon Cancer Cells: a Crosstalk Interrupted by Vitamin D3

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2009 Aug 25

PMID 19701245

Citations 141

Authors

P Kaler

L Augenlicht

L Klampfer

Affiliations

Soon will be listed here.

Abstract

Tumor-associated macrophages mediate the link between inflammation and cancer progression. Here, we showed that macrophage-derived soluble factors induce canonical Wnt signaling in colon cancer cells and promote their growth. Tumor cells induced the release of interleukin (IL)-1beta from macrophages, which induced phosphorylation of GSK3beta, stabilized beta-catenin, enhanced T-cell factor (TCF)-dependent gene activation and induced the expression of Wnt target genes in tumor cells. Neutralization experiments using anti-IL-1beta-specific antibodies, or silencing of IL-1beta in THP1 macrophages, showed that IL-1beta was required for macrophages to induce Wnt signaling and to support the growth of tumor cells. Constitutive activation of signal transducer and activator of transcription (STAT)1 in THP1 macrophages was essential for the induction of IL-1beta and thus for the activation of beta-catenin signaling in tumor cells. Vitamin D3, an effective chemopreventive agent, interrupted this crosstalk by blocking the constitutive activation of STAT1 and the production of IL-1beta in macrophages, and therefore-in a vitamin D receptor-dependent manner-inhibited the ability of macrophages to activate Wnt signaling in colon carcinoma cells. Our data therefore established that vitamin D3 exerts its chemopreventive activity by interrupting a crosstalk between tumor epithelial cells and the tumor microenvironment.

Citing Articles

Ferroptotic Neutrophils Induce Immunosuppression and Chemoresistance in Breast Cancer.

Zeng W, Zhang R, Huang P, Chen M, Chen H, Zeng X Cancer Res. 2024; 85(3):477-496.

PMID: 39531510 PMC: 11786957. DOI: 10.1158/0008-5472.CAN-24-1941.

Novel Oncogenic Value of C10orf90 in Colon Cancer Identified as a Clinical Diagnostic and Prognostic Marker.

Ruan C, Zhang Y, Chen D, Zhu M, Yang P, Zhang R Int J Mol Sci. 2024; 25(19).

PMID: 39408824 PMC: 11476934. DOI: 10.3390/ijms251910496.

SPRi Biosensor for Simultaneous Determination of HIF-1α, Angiopoietin-2, and Interleukin-1β in Blood Plasma.

Zielinska Z, Oldak L, Guszcz T, Hermanowicz A, Gorodkiewicz E Sensors (Basel). 2024; 24(17).

PMID: 39275392 PMC: 11397757. DOI: 10.3390/s24175481.

IL-1β mediates Candida tropicalis-induced immunosuppressive function of MDSCs to foster colorectal cancer.

Zhang Z, Chen Y, Pan X, Li P, Ren Z, Wang X Cell Commun Signal. 2024; 22(1):408.

PMID: 39164774 PMC: 11337875. DOI: 10.1186/s12964-024-01771-y.

ATG16L1 in myeloid cells limits colorectal tumor growth in mice infected with colibactin-producing via decreasing inflammasome activation.

Salesse L, Duval A, Sauvanet P, Da Silva A, Barnich N, Godfraind C Autophagy. 2024; 20(10):2186-2204.

PMID: 38818900 PMC: 11423662. DOI: 10.1080/15548627.2024.2359770.

References

Klampfer L, Huang J, Shirasawa S, Sasazuki T, Augenlicht L . Histone deacetylase inhibitors induce cell death selectively in cells that harbor activated kRasV12: The role of signal transducers and activators of transcription 1 and p21. Cancer Res. 2007; 67(18):8477-85. DOI: 10.1158/0008-5472.CAN-07-0210. View

Etoh T, Shibuta K, Barnard G, Kitano S, Mori M . Angiogenin expression in human colorectal cancer: the role of focal macrophage infiltration. Clin Cancer Res. 2000; 6(9):3545-51. View

Tsuchiya S, Kobayashi Y, Goto Y, Okumura H, Nakae S, Konno T . Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982; 42(4):1530-6. View

Klampfer L, Swaby L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L . Oncogenic Ras increases sensitivity of colon cancer cells to 5-FU-induced apoptosis. Oncogene. 2005; 24(24):3932-41. DOI: 10.1038/sj.onc.1208552. View

Palmer H, Gonzalez-Sancho J, Espada J, Berciano M, Puig I, Baulida J . Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J Cell Biol. 2001; 154(2):369-87. PMC: 2150773. DOI: 10.1083/jcb.200102028. View

Pull S, Doherty J, Mills J, Gordon J, Stappenbeck T . Activated macrophages are an adaptive element of the colonic epithelial progenitor niche necessary for regenerative responses to injury. Proc Natl Acad Sci U S A. 2004; 102(1):99-104. PMC: 544052. DOI: 10.1073/pnas.0405979102. View

Kumagai T, OKelly J, Said J, Koeffler H . Vitamin D2 analog 19-nor-1,25-dihydroxyvitamin D2: antitumor activity against leukemia, myeloma, and colon cancer cells. J Natl Cancer Inst. 2003; 95(12):896-905. DOI: 10.1093/jnci/95.12.896. View

Maeda S, Hsu L, Liu H, Bankston L, Iimura M, Kagnoff M . Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005; 307(5710):734-8. DOI: 10.1126/science.1103685. View

Biswas S, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M . A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood. 2005; 107(5):2112-22. DOI: 10.1182/blood-2005-01-0428. View

10.

Shah S, Islam M, Dakshanamurthy S, Rizvi I, Rao M, Herrell R . The molecular basis of vitamin D receptor and beta-catenin crossregulation. Mol Cell. 2006; 21(6):799-809. DOI: 10.1016/j.molcel.2006.01.037. View

11.

Brabletz T, Jung A, Hermann K, Gunther K, Hohenberger W, Kirchner T . Nuclear overexpression of the oncoprotein beta-catenin in colorectal cancer is localized predominantly at the invasion front. Pathol Res Pract. 1998; 194(10):701-4. DOI: 10.1016/s0344-0338(98)80129-5. View

12.

Klampfer L, Huang J, Sasazuki T, Shirasawa S, Augenlicht L . Inhibition of interferon gamma signaling by the short chain fatty acid butyrate. Mol Cancer Res. 2003; 1(11):855-62. View

13.

Tsukada J, Waterman W, Koyama Y, Webb A, Auron P . A novel STAT-like factor mediates lipopolysaccharide, interleukin 1 (IL-1), and IL-6 signaling and recognizes a gamma interferon activation site-like element in the IL1B gene. Mol Cell Biol. 1996; 16(5):2183-94. PMC: 231206. DOI: 10.1128/MCB.16.5.2183. View

14.

Robsahm T, Tretli S, Dahlback A, Moan J . Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control. 2004; 15(2):149-58. DOI: 10.1023/B:CACO.0000019494.34403.09. View

15.

Lamprecht S, Lipkin M . Chemoprevention of colon cancer by calcium, vitamin D and folate: molecular mechanisms. Nat Rev Cancer. 2003; 3(8):601-14. DOI: 10.1038/nrc1144. View

16.

Lin W, Karin M . A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 2007; 117(5):1175-83. PMC: 1857251. DOI: 10.1172/JCI31537. View

17.

Tu S, Bhagat G, Cui G, Takaishi S, Kurt-Jones E, Rickman B . Overexpression of interleukin-1beta induces gastric inflammation and cancer and mobilizes myeloid-derived suppressor cells in mice. Cancer Cell. 2008; 14(5):408-19. PMC: 2586894. DOI: 10.1016/j.ccr.2008.10.011. View

18.

Newmark H, Lipkin M . Calcium, vitamin D, and colon cancer. Cancer Res. 1992; 52(7 Suppl):2067s-2070s. View

19.

Oyama T, Yamada Y, Hata K, Tomita H, Hirata A, Sheng H . Further upregulation of beta-catenin/Tcf transcription is involved in the development of macroscopic tumors in the colon of ApcMin/+ mice. Carcinogenesis. 2008; 29(3):666-72. DOI: 10.1093/carcin/bgn001. View

20.

Fichera A, Little N, Dougherty U, Mustafi R, Cerda S, Li Y . A vitamin D analogue inhibits colonic carcinogenesis in the AOM/DSS model. J Surg Res. 2007; 142(2):239-45. DOI: 10.1016/j.jss.2007.02.038. View