Potential interaction between lysophosphatidic acid and tumor-associated macrophages in ovarian carcinoma

Ying Feng,Ran Cui,Huimin Bai,Chongdong Liu,Meizhu Xiao,Zihan Zhang,Shuzhen Wang,Xuan Jiang,Zhenyu Zhang

doi:10.1186/s12950-020-00254-4

Abstract

Ovarian carcinoma is the deadliest type of gynecological cancer. The unique tumor microenvironment enables specific and efficient metastasis, weakens immunological monitoring, and mediates drug resistance. Tumor associated macrophages (TAMs) are a crucial part of the TME and are involved in various aspects of tumor behavior. Lysophosphatidic acid (LPA) is elevated in the blood of ovarian carcinoma patients, as well as in the tumor tissues and ascites, which make it a useful biomarker and a potential therapeutic target. Recent studies have shown that LPA transforms monocytes into macrophages and regulates the formation of macrophages through the AKT/mTOR pathway, and PPAR γ is a major regulator of LPA-derived macrophages. In addition, TAMs synthesize and secrete LPA and express LPA receptor (LPAR) on the surface. With these data in mind, we hypothesize that LPA can convert monocytes directly into TAMs in the microenvironment of ovarian cancer. LPA may mediate TAM formation by activating the PI3K/AKT/mTOR signaling pathway through LPAR on the cell surface, which may also affect the function of PPAR γ, leading to increased LPA production by TAMs. Thus, LPA and TAMs form a vicious circle that affects the malignant behavior of ovarian cancer.

Highlights

Ovarian carcinoma is the most common cause of mortality from gynecological tumors and the 5th leading cause of cancer death in women [1]
Lysophosphatidic acid (LPA) and Tumor associated macrophages (TAMs) play similar roles LPA regulates a variety of tumor-promoting factors and inflammatory factors in epithelial ovarian cancer, including IL-6, IL-8, vascular endothelial growth factor (VEGF), matrix metallopeptidases (MMPs), CXCL12, cytochrome c oxidase subunit 2 (COX2), urokinase plasminogen activator (uPA), cyclin D1, CXCL1 [43]
Macrophages produce many factors that contribute to tumor growth, including VEGF, IL1, IL-6, nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and macrophage colony-stimulating factor (M-CSF) [44, 45]

Summary

Introduction

Ovarian carcinoma is the most common cause of mortality from gynecological tumors and the 5th leading cause of cancer death in women [1]. * Correspondence: chongdongliu2015@163.com; zhenyuzhang2015@163.com 1Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital, Capital Medical University, No 8, North Road of Workers Stadium, Chaoyang District, Beijing 100020, China Full list of author information is available at the end of the article an important component of the TME, tumor associated macrophages (TAMs) make a crucial part in ovarian cancer progression, chemotherapeutic resistance, immunosuppression and prognosis. LPA can promote tumor survival and proliferation, cisplatin resistance and increase the production of urokinase plasminogen activator (uPA), additional LPA generation and vascular endothelial growth factor (VEGF) in ovarian cancer.

Results

Conclusion