TITLE

Tumor-Produced Versican V1 Enhances hCAP18/LL-37 Expression in Macrophages through Activation of TLR2 and Vitamin D3 Signaling to Promote Ovarian Cancer Progression In Vitro

AUTHOR(S)
Li, Dong; Wang, Xuan; Wu, Jun-Lu; Quan, Wen-Qiang; Ma, Li; Yang, Fan; Wu, Kai-Yin; Wan, Hai-Ying
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Tumor-associated macrophages have been shown to promote tumor growth. They may have an obligatory function in angiogenesis, invasion, and metastasis through release of inflammatory mediators. Their presence in ovarian cancer has been correlated with poor prognosis in these patients. The human cationic antimicrobial protein-18 (hCAP18)/LL-37 was originally identified as an effector molecule of the innate immune system. It is released by innate immune cells, such as macrophages, to combat microorganisms. Previous studies have characterized the hCAP18/LL-37 as a growth factor that has been shown to promote ovarian tumor progression. However, the role hCAP18/LL-37 has in macrophage-promoted ovarian tumor development and how its expression is controlled in this context remains poorly understood. Here, we demonstrate in co-culture experiments of macrophages and ovarian cancer cells a significant increase in the in vitro proliferation and invasiveness of the tumor cells is observed. These enhanced growth and invasion properties correlated with hCAP18/LL-37 induction. HCAP18/LL-37 expression was diminished by addition of two neutralizing antibodies, TLR2 or TLR6, as well as Cyp27B1 or VDR inhibitors. Furthermore, either the TLR2 or TLR6 antibody reduced vitamin D3 signaling and tumor cell progression in vitro. Addition of Cyp27B1 or VDR inhibitors abrogated TLR2/6 activation-induced expression of hCAP18/LL-37 in macrophages. Knockdown of tumor-produced versican V1 by RNAi in these tumor cells led to a decreased induction of hCAP18/LL-37 in macrophages. Versican V1 knockdown also inhibited TLR2 and vitamin D3 signaling, as well as growth and invasiveness of these tumor cells in the in vitro co-culture. In summary, we have found that versican V1 enhances hCAP18/LL-37 expression in macrophages through activation of TLR2 and subsequent vitamin D-dependent mechanisms which promote ovarian tumor progression in vitro.
ACCESSION #
87624772

 

Related Articles

  • The Effect of Toll-Like Receptor 4 on Macrophage Cytokines During Endotoxin Induced Uveitis. Shuo Yang; Hong Lu; Jing Wang; Xin Qi; Xuhui Liu; Xiaolong Zhang // International Journal of Molecular Sciences;Jun2012, Vol. 13 Issue 6, p7508 

    Toll-like receptor 4 (TLR4) signal activation of macrophages can lead to endotoxin-induced uveitis (EIU). Previously, our research group has demonstrated a higher expression of TLR4 in vivo during EIU than normal. In this study, we analyzed levels of peritoneal macrophage cytokines from C3H/HeN...

  • Toll-like receptors in ovarian cancer as targets for immunotherapies. Muccioli, Maria; Benencia, Fabian // Frontiers in Immunology;Jul2014, Vol. 5, p1 

    In the last decade, it has become apparent that toll-like receptor (TLR) signaling can play an important role in ovarian cancer (OC) progression. Interestingly, TLR activation in immune cells can help activate an anti-tumor response, while TLR signaling in tumor cells themselves is often...

  • The Role of Nuclear β-Catenin Accumulation in the Twist2-Induced Ovarian Cancer EMT. Mao, Yubin; Xu, Jinfei; Li, Zhihan; Zhang, Nini; Yin, Hao; Liu, Zuguo // PLoS ONE;Nov2013, Vol. 8 Issue 11, p1 

    Background: Twist2 has been shown to promote human tumor invasion as in breast cancer and cervical cancer. However, whether Twist2 promotes human ovarian cancer progression remains to be elucidated. Here, we investigate the role of Twist2 in ovarian cancer invasion and metastasis as well as the...

  • Effect of 1,25-dihydroxy vitamin D3 on toll-like receptor gene expression in neutrophils of pulmonary tuberculosis. Harishankar, M.; Afsal, K.; Meenakshi, N.; Selvaraj, P. // Current Science (00113891);8/25/2014, Vol. 107 Issue 4, p642 

    We studied the effect of 1,25-dihydroxy vitamin D3 [1,25(OH)2D3] on toll-like receptor (TLR) gene expression in neutrophils cultured with Mycobacterium tuberculosis (Mtb) with or without 1,25(OH)2D3 in pulmonary tuberculosis patients and healthy controls. 1,25(OH)2D3 significantly increased the...

  • GPHR-Dependent Functions of the Golgi Apparatus Are Essential for the Formation of Lamellar Granules and the Skin Barrier. Tarutani, Masahito; Nakajima, Kimiko; Uchida, Yoshikazu; Takaishi, Mikiro; Goto-Inoue, Naoko; Ikawa, Masahito; Setou, Mitsutoshi; Kinoshita, Taroh; Elias, Peter M; Sano, Shigetoshi; Maeda, Yusuke // Journal of Investigative Dermatology;Aug2012, Vol. 132 Issue 8, p2019 

    The lumen of the Golgi apparatus is regulated to be weakly acidic, which is critical for its functions. The Golgi pH regulator (GPHR) is an anion channel essential for normal acidification of the Golgi apparatus, and is therefore required for its functions. The Golgi apparatus has been thought...

  • Activating transcription factor 2 expression mediates cell proliferation and is associated with poor prognosis in human non-small cell lung carcinoma. ZHENYU YOU; YONG ZHOU; YULING GUO; WENYAN CHEN; SHAOQING CHEN; XIAOLANG WANG // Oncology Letters;Jan2016, Vol. 11 Issue 1, p760 

    Activating transcription factor 2 (ATF2) is a member of the cAMP response element binding protein family that heterodimerizes and activates other transcription factors involved in stress and DNA damage responses, growth, differentiation and apoptosis. ATF2 has been investigated as a potential...

  • LL-37-induced host cell cytotoxicity depends on cellular expression of the globular C1q receptor (p33). Svensson, Daniel; Wilk, Laura; Mörgelin, Matthias; Herwald, Heiko; Nilsson, Bengt-Olof // Biochemical Journal;1/1/2016, Vol. 473 Issue 1, p87 

    The human host-defence peptide (HDP) LL-37 not only displays anti-microbial activity but also immune-modulating properties that trigger intracellular signalling events in host cells. Since the cytolytic activity of high LL-37 concentrations affects cell viability, the function of LL-37 requires...

  • Rosacea: The Blessing of the Celts - An Approach to Pathogenesis Through Translational Research. MELNIK, Bodo C. // Acta Dermato-Venereologica;Feb2016, Vol. 96 Issue 2, p147 

    Increased expression of cathelicidin antimicrobial peptide (CAMP) is related to the pathogenesis of rosacea. CAMP plays a crucial role in antimicrobial defences, such as the killing of mycobacteria. CAMP gene expression is regulated by vitamin D-dependent (VDR) and vitamin D-independent...

  • A Mathematical Model of CR3/TLR2 Crosstalk in the Context of Francisella tularensis Infection. Leander, Rachel; Dai, Shipan; Schlesinger, Larry S.; Friedman, Avner // PLoS Computational Biology;Nov2012, Vol. 8 Issue 11, p1 

    Complement Receptor 3 (CR3) and Toll-like Receptor 2 (TLR2) are pattern recognition receptors expressed on the surface of human macrophages. Although these receptors are essential components for recognition by the innate immune system, pathogen coordinated crosstalk between them can suppress the...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics