Gene expression profiles of lysophosphatidic acid‐related molecules in the prostate: Relevance to prostate cancer and benign hyperplasia

Abstract

By acting via LPA3, LPA may play an important role in the development of prostate cancer. Switching of LPA receptor expression from LPA3 to LPA1, may be involved in prostate cancer progression and/or androgen independence. LPA may also play a key role in the development of benign prostatic hyperplasia.

LPA receptor signaling: pharmacology, physiology, and pathophysiology

“…LPA 3 may play a complementary role, initiating invasion and metastasis of the same cancer cell types (295)(296)(297).…”

Lysophosphatidic acid receptors (LPARs): Potential targets for the treatment of neuropathic pain

“…LPA can be produced by platelets (Eichholtz et al, 1993), fibroblasts (Fukami and Takenawa, 1992), mitotic neurons (Fukushima et al, 2000), astrocytes (Savaskan et al, 2007) and also cancer cells (Zhao et al, 2010). High concentrations of LPA have been observed in several pathological conditions such as atherosclerosis (Smyth et al, 2014), traumatic brain injury (Crack et al, 2014), spinal cord injury (Santos- Nogueira et al, 2015), different types of cancer (Eder et al, 2000;Lee and Yun, 2010;Zeng et al, 2009;Zhao et al, 2010), neuropsychiatric disorders (Yung et al, 2014) and neuropathic pain (Ahn et al, 2009;Fujita et al, 2007). Production of LPA during inflammation promotes wound-healing and acts to control the proinflammatory environment.…”

Effects of Lysophospholipids on Tumor Microenvironment

“…It is involved in multiple important stages of cancer development [69,70], induces the release of angiogenic factors such as vascular endothelial growth factor [71], and is involved in neovascularization and tumor growth and survival. An inhibitor of LPA signaling pathway induced tumor regression and loss of vascularity in a model of tumor growth [72] Also, LPA 2 as well as LPA 1 and 3 expression is high in tumor cell lines [73,74]. In contrast, LPA 2 deficiency provides protection against cancer development [75], whereas LPA 1 and LPA 3 mRNA are elevated in epithelium derived from prostate cancers compared to benign glands [74].…”

“…An inhibitor of LPA signaling pathway induced tumor regression and loss of vascularity in a model of tumor growth [72] Also, LPA 2 as well as LPA 1 and 3 expression is high in tumor cell lines [73,74]. In contrast, LPA 2 deficiency provides protection against cancer development [75], whereas LPA 1 and LPA 3 mRNA are elevated in epithelium derived from prostate cancers compared to benign glands [74]. This has led to suggesting that a switch from LPA 1 to LPA 3 may be in involved in cancer progression [74], while later expression of LPA 1 might lead to metastatic development [73,76].…”