AF1q inhibited T cell attachment to breast cancer cell by attenuating Intracellular Adhesion Molecule-1 expression

Abstract

Aim: To investigate whether AF1q, overexpressed in metastatic cells compared with the primary tumor cells, plays a pivotal role in breast cancer metastasis.

Methods: To investigate whether AF1q has a responsibility in the acquisition of a metastatic phenotype, we performed RNA-sequencing (RNA-Seq) to identify the gene signature and applied the Metacore direct interactions network building algorithm with the top 40 amplicons of RNA-Seq.

Results: Most genes were directly linked with intercellular adhesion molecule-1 (ICAM-1). Likewise, we identified that ICAM-1 expression is attenuated in metastatic cells compared to primary tumor cells. Moreover, overexpression of AF1q attenuated ICAM-1 expression, whereas suppression of AF1q elicited the opposite effect. AF1q had an effect on ICAM-1 promoter region and regulated its transcription. Decreased ICAM-1 expression affected the attachment of T cells to a breast cancer cell monolayer. We confirmed the finding by performing the analysis on Burkitt’s lymphoma.

Conclusion: Attenuation of ICAM-1 by AF1q on tumor cells disadvantages host anti-tumor defenses through the trafficking of lymphocytes, which affects tumor progression and metastasis.

Keywords

MLLT11 / AF1q / intercellular adhesion molecule-1 / breast cancer / metastasis / RNA-sequencing

References

[1] Tse W,Chen HS.A novel gene, AF1q, fused to MLL in t(1;11) (q21;q23), is specifically expressed in leukemic and immature hematopoietic cells..Blood1995;85:650-6

[2] Park J,Schreiber M,Merkel O.AF1q is a novel TCF7 co-factor which activates CD44 and promotes breast cancer metastasis..Oncotarget2015;6:20697-710 PMCID:PMC4653036

[3] Anastas JN.WNT signalling pathways as therapeutic targets in cancer..Nat Rev Cancer2013;13:11-26

[4] Park J,Joh J,Miller DM.MLLT11/AF1q boosts oncogenic STAT3 activity through Src-PDGFR tyrosine kinase signaling..Oncotarget2016;7:43960-73 PMCID:PMC5190071

[5] Zimmerman T.Inhibitors targeting the LFA-1/ICAM-1 cell-adhesion interaction: design and mechanism of action..Curr Pharm Des2008;14:2128-39

[6] Lawson C.ICAM-1 signaling in endothelial cells..Pharmacol Rep2009;61:22-32

[7] Ogawa Y,Nakata B,Sawada T.Expression of intercellular adhesion molecule-1 in invasive breast cancer reflects low growth potential, negative lymph node involvement, and good prognosis..Clin Cancer Res1998;4:31-6

[8] Maeda K,Sawada T,Yashiro M.Expression of intercellular adhesion molecule-1 and prognosis in colorectal cancer..Oncol Rep2002;9:511-4

[9] Anastassiou G,Stang A,Heiligenhaus A.Expression of the cell adhesion molecules ICAM-1, VCAM-1 and NCAM in uveal melanoma: a clinicopathological study..Oncology2000;58:83-8

[10] Rosette C,Oeth P,Kammerer S.Role of ICAM1 in invasion of human breast cancer cells..Carcinogenesis2005;26:943-50

[11] Kotteas EA,Gkiozos I,Tsoukalas G.The intercellular cell adhesion molecule-1 (icam-1) in lung cancer: implications for disease progression and prognosis..Anticancer Res2014;34:4665-72

[12] Melis M,Melodia A,Gjomarkaj M.ICAM-1 expression by lung cancer cell lines: effects of upregulation by cytokines on the interaction with LAK cells..Eur Respir J1996;9:1831-8

[13] Haustein M,Linnebacher M,Hinz B.Cannabinoids increase lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1..Biochem Pharmacol2014;92:312-25

[14] Jenkins DE,Oei Y,Purchio T.Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice..Breast Cancer Res2005;7:R444-54 PMCID:PMC1175057

[15] Park JO,Hong ST.A new method for transduction of mesenchymal stem cells using mechanical agitation..Mol Cells2009;28:515-20

[16] Gregory CD,Edwards CF.Downregulation of cell adhesion molecules LFA-3 and ICAM-1 in Epstein-Barr virus-positive Burkitt's lymphoma underlies tumor cell escape from virus-specific T cell surveillance..J Exp Med1988;167:1811-24 PMCID:PMC2189677

[17] Melotti P,Tamanini A,Pavirani A.Activation of NF-kB mediates ICAM-1 induction in respiratory cells exposed to an adenovirus-derived vector..Gene Ther2001;8:1436-42

[18] Nejak-Bowen K,Monga SP.Beta-catenin-NF-kappaB interactions in murine hepatocytes: a complex to die for..Hepatology2013;57:763-74 PMCID:PMC3566301

[19] Ma B.Crosstalk between Wnt/beta-catenin and NF-kappaB signaling pathway during inflammation..Front Immunol2016;7:378 PMCID:PMC5031610

[20] Deng J,Wang HY,Wen Y.Beta-catenin interacts with and inhibits NF-kappa B in human colon and breast cancer..Cancer Cell2002;2:323-34

[21] Hogg N,Willenbrock F.The insider's guide to leukocyte integrin signalling and function..Nat Rev Immunol2011;11:416-26

[22] Adams DH.Leucocyte-endothelial interactions and regulation of leucocyte migration..Lancet1994;343:831-6

[23] Butcher EC.Lymphocyte homing and homeostasis..Science1996;272:60-6

[24] Lanitis E,Coukos G.Targeting the tumor vasculature to enhance T cell activity..Curr Opin Immunol2015;33:55-63 PMCID:PMC4896929

[25] Bouzin C.Targeting tumor stroma and exploiting mature tumor vasculature to improve anti-cancer drug delivery..Drug Resist Updat2007;10:109-20

[26] Griffioen AW,Martinotti S,Groenewegen G.Endothelial intercellular adhesion molecule-1 expression is suppressed in human malignancies: the role of angiogenic factors..Cancer Res1996;56:1111-17

[27] Lanitis E,Irving M.Mechanisms regulating T-cell infiltration and activity in solid tumors..Ann Oncol2017;28:xii18-32

[28] Azuma A,Matsuda H,Niitani H.Induction of intercellular adhesion molecule 1 on small cell lung carcinoma cell lines by gamma-interferon enhances spontaneous and bispecific anti-CD3 x antitumor antibody-directed lymphokine activated killer cell cytotoxicity..Cancer Res1992;52:4890-4

[29] Mentzer SJ,Springer TA.Intercellular adhesion molecule-1 (ICAM-1) is involved in the cytolytic T lymphocyte interaction with a human synovial cell line..J Cell Physiol1988;137:173-8

[30] Anichini A,Alberti S,Parmiani G.T-cell-receptor engagement and tumor ICAM-1 up-regulation are required to by-pass low susceptibility of melanoma cells to autologous CTL-mediated lysis..Int J Cancer1993;53:994-1001

[31] Anichini A,Supino R.Human melanoma cells with high susceptibility to cell-mediated lysis can be identified on the basis of ICAM-1 phenotype, VLA profile and invasive ability..Int J Cancer1990;46:508-15