IFNγ induces JAK1/STAT1/p65 NFκB-dependent interleukin-8 expression in ovarian cancer cells, resulting in their increased migration

被引：12

作者：

Padmanabhan, Sveta ^{[1
]}

Gaire, Bijaya ^{[1
]}

Zou, Yue ^{[1
]}

Uddin, Mohammad M. ^{[1
]}

DeLeon, Daniel ^{[1
]}

Vancurova, Ivana ^{[1
]}

机构：

[1] St Johns Univ, Dept Biol Sci, Queens, NY 11439 USA

来源：

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY | 2021年 / 141卷

基金：

美国国家卫生研究院;

关键词：

Interferon-gamma; Interleukin-8; JAK1; STAT1; p65NF kappa B; Ovarian cancer; Cell invasion; REDUCED CLINICAL BENEFIT; INTERFERON-GAMMA; SERUM INTERLEUKIN-8; 1ST-LINE TREATMENT; IMMUNE-RESPONSES; RANDOMIZED-TRIAL; REGULATORY T; ACETYLATION; PROGRESSION; MELANOMA;

D O I：

10.1016/j.biocel.2021.106093

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Interferon-gamma (IFN gamma) is a pleiotropic cytokine that has a crucial role in immune response and tumor immunity. Because of its anti-tumor effects, IFN gamma has been used in cancer treatment. However, IFN gamma also has tumor-promoting functions that are less well understood. Here, we show that IFN gamma induces expression of the pro-inflammatory and pro-angiogenic chemokine interleukin-8 (IL-8, CXCL8) in ovarian cancer (OC) cells. The IFN gamma-induced IL-8 expression is dependent on JAK1, STAT1, and p65 NF kappa B, and is associated with an increased occupancy of K314/315 acetylated p65 NF kappa B and Ser-727 phosphorylated STAT1 at the IL-8 promoter. Neutralization of IL-8 using anti-IL-8 antibody reduces IFN gamma-induced migration of OC cells, and their invasion ability in 3D spheroids. Together, these findings identify IL-8 as a novel target induced by IFN gamma/JAK1/STAT1/ p65 NF kappa B signaling, and indicate that the IFN gamma-induced IL-8 contributes to IFN gamma pro-tumorigenic effects in ovarian cancer cells.

引用

页数：10

共 56 条

[1] IFN-γ from lymphocytes induces PD-L1 expression and promotes progression of ovarian cancer [J].

Abiko, K. ;

Matsumura, N. ;

Hamanishi, J. ;

Horikawa, N. ;

Murakami, R. ;

Yamaguchi, K. ;

Yoshioka, Y. ;

Baba, T. ;

Konishi, I. ;

Mandai, M. .

BRITISH JOURNAL OF CANCER, 2015, 112 (09) :1501-1509

[2] Randomized phase 3 trial of interferon gamma-1b plus standard carboplatin/paclitaxel versus carboplatin/paclitaxel alone for first-line treatment of advanced ovarian and primary peritoneal carcinomas: Results from a prospectively designed analysis of progression-free survival [J].

Alberts, David S. ;

Marth, Christian ;

Alvarez, Ronald D. ;

Johnson, Gary ;

Bidzinski, Mariusz ;

Kardatzke, David R. ;

Bradford, Williamson Z. ;

Loutit, Jeff ;

Kim, David H. ;

Clouser, Mary C. ;

Markman, Maurie .

GYNECOLOGIC ONCOLOGY, 2008, 109 (02) :174-181

[3] Interferon γ and Its Important Roles in Promoting and Inhibiting Spontaneous and Therapeutic Cancer Immunity [J].

Alspach, Elise ;

Lussier, Danielle M. ;

Schreiber, Robert D. .

COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2019, 11 (03)

[4] IFN-γ orchestrates tumor elimination, tumor dormancy, tumor escape, and progression [J].

Aqbi, Hussein F. ;

Wallace, Matthew ;

Sappal, Samay ;

Payne, Kyle K. ;

Manjili, Masoud H. .

JOURNAL OF LEUKOCYTE BIOLOGY, 2018, 103 (06) :1219-1223

[5] IL-8 and cancer prognosis on immunotherapy [J].

Bakouny, Ziad ;

Choueiri, Toni K. .

NATURE MEDICINE, 2020, 26 (05) :650-651

[6] STAT1-NFκB crosstalk triggered by interferon gamma regulates noradrenaline-induced pineal hormonal production [J].

Barbosa Lima, Leila Eliza ;

Muxel, Sandra Marcia ;

Kinker, Gabriela S. ;

Carvalho-Sousa, Claudia Emanuele ;

Cruz-Machado, Sanseray da Silveira ;

Markus, Regina P. ;

Carlos Magno Fernandes, Pedro Augusto .

JOURNAL OF PINEAL RESEARCH, 2019, 67 (03)

[7] Interferon-γ-induced activation of JAK1 and JAK2 suppresses tumor cell susceptibility to NK cells through upregulation of PD-L1 expression [J].

Bellucci, Roberto ;

Martin, Allison ;

Bommarito, Davide ;

Wang, Kathy ;

Hansen, Steen H. ;

Freeman, Gordon J. ;

Ritz, Jerome .

ONCOIMMUNOLOGY, 2015, 4 (06)

[8] Opposing Functions of Interferon Coordinate Adaptive and Innate Immune Responses to Cancer Immune Checkpoint Blockade [J].

Benci, Joseph L. ;

Johnson, Lexus R. ;

Choa, Ruth ;

Xu, Yuanming ;

Qiu, Jingya ;

Zhou, Zilu ;

Xu, Bihui ;

Ye, Darwin ;

Nathanson, Katherine L. ;

June, Carl H. ;

Wherry, E. John ;

Zhang, Nancy R. ;

Ishwaran, Hemant ;

Hellmann, Matthew D. ;

Wolchok, Jedd D. ;

Kambayashi, Taku ;

Minn, Andy J. .

CELL, 2019, 178 (04) :933-+

[9] Tumor Interferon Signaling Regulates a Multigenic Resistance Program to Immune Checkpoint Blockade [J].

Benci, Joseph L. ;

Xu, Bihui ;

Qiu, Yu ;

Wu, Tony J. ;

Dada, Hannah ;

Twyman-Saint Victor, Christina ;

Cucolo, Lisa ;

Lee, David S. M. ;

Pauken, Kristen E. ;

Huang, Alexander C. ;

Gangadhar, Tara C. ;

Amaravadi, Ravi K. ;

Schuchter, Lynn M. ;

Feldman, Michael D. ;

Ishwaran, Hemant ;

Vonderheide, Robert H. ;

Maity, Amit ;

Wherry, E. John ;

Minn, Andy J. .

CELL, 2016, 167 (06) :1540-+

[10] Phase I trial of HuMax-IL8 (BMS-986253), an anti-IL-8 monoclonal antibody, in patients with metastatic or unresectable solid tumors [J].

Bilusic, Marijo ;

Heery, Christopher R. ;

Collins, Julie M. ;

Donahue, Renee N. ;

Palena, Claudia ;

Madan, Ravi A. ;

Karzai, Fatima ;

Marte, Jennifer L. ;

Strauss, Julius ;

Gatti-Mays, Margaret E. ;

Schlom, Jeffrey ;

Gulley, James L. .

JOURNAL FOR IMMUNOTHERAPY OF CANCER, 2019, 7 (01)

← 1 2 3 4 5 6 →