4.4 Review

Revisiting the role of lysophosphatidic acid in stem cell biology

Journal

EXPERIMENTAL BIOLOGY AND MEDICINE
Volume 246, Issue 16, Pages 1802-1809

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/15353702211019283

Keywords

Cancer stem cells; therapy resistance; chemoresistance; metastasis; lysophosphatidic acid; autotaxin; mesenchymal stem cells; somatic stem cells; intestinal stem cells; stem cell therapy

Funding

  1. William and Ella Owens Medical Research Foundation
  2. University of Tennessee CORNET grant
  3. National Cancer Institute [CA092160]
  4. National Institute of Allergy and Infectious Diseases [AI107331, 1U19AI150574]
  5. Harriet Van Vleet endowment
  6. Memphis Institute of Regenerative Medicine (MIRM) Institute Project 4 pilot grant
  7. [MOST-109-2917-I-564-029]

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Stem cells, including embryonic stem cells (ESC), somatic stem cells (SSC), and cancer stem cells (CSC), have unique biological characteristics and play important roles in cell differentiation and tissue regeneration. Research efforts focus on understanding the role of CSC in cancer development and identifying new therapeutic strategies.
Stem cells possess unique biological characteristics such as the ability to self-renew and to undergo multilineage differentiation into specialized cells. Whereas embryonic stem cells (ESC) can differentiate into all cell types of the body, somatic stem cells (SSC) are a population of stem cells located in distinct niches throughout the body that differentiate into the specific cell types of the tissue in which they reside in. SSC function mainly to restore cells as part of normal tissue homeostasis or to replenish cells that are damaged due to injury. Cancer stem-like cells (CSC) are said to be analogous to SSC in this manner where tumor growth and progression as well as metastasis are fueled by a small population of CSC that reside within the corresponding tumor. Moreover, emerging evidence indicates that CSC are inherently resistant to chemo- and radiotherapy that are often the cause of cancer relapse. Hence, major research efforts have been directed at identifying CSC populations in different cancer types and understanding their biology. Many factors are thought to regulate and maintain cell stemness, including bioactive lysophospholipids such as lysophosphatidic acid (LPA). In this review, we discuss some of the newly discovered functions of LPA not only in the regulation of CSC but also normal SSC, the similarities in these regulatory functions, and how these discoveries can pave way to the development of novel therapies in cancer and regenerative medicine.

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