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Stem Cell Adhesion Molecules


Overview of Stem Cell Adhesion Molecules

Before talking about stem cell adhesion molecules, let’s take a look at cell adhesion molecules. Cell adhesion molecules (CAM) are molecules produced by cells that mediate cell-to-cell or cell-to-matrix contact and binding, and are mostly glycoproteins distributed on the cell surface. According to the structural characteristics of adhesion molecules can be divided into the following categories: integrin family, immunoglobulin superfamily, selectin family and cadherin family, in addition to some unclassified adhesion molecules, there are many types of adhesion molecules. Adhesion molecules participate in many important physiological and pathological processes in the body by participating in cell signal transduction, mediating cell expansion and movement, affecting cell growth and differentiation, in the form of binding of ligands and receptors. Moderate expression of adhesion molecules and their stable cell adhesion are essential for life activities and self-stability. However, its expression or dysfunction and the resulting abnormal cell adhesion can cause various diseases and pathological damage in the body. According to previous studies, stem cell adhesion molecules play an important role in the differentiation and migration of stem cells, and stem cells’ attachment is also closely related to it.

Structure of Stem Cell Adhesion Molecules

The structure of stem cell adhesion molecules

Figure 1. The structure of stem cell adhesion molecules

Cell adhesion molecules (of course including stem cell adhesion molecules) are transmembrane glycoproteins, and the molecular structure consists of three parts: (1) extracellular domain, the N-terminal part of the peptide chain, with a sugar chain, responsible for the recognition of the ligand; (2) transmembrane region, mostly one-time transmembrane; (3) the cytoplasmic region, the C-terminal portion of the peptide chain, is generally small, or directly linked to the skeleton component under the plasma membrane, or linked to intracellular chemical signaling molecules to activate the signal transduction pathway. The action of most cell adhesion molecules depends on divalent cations such as Ca2+, Mg2+. There are three modes of action of cell adhesion molecules: (1) mutual recognition and binding between homologous CAM molecules on the surface of two adjacent cells (affinity adhesion); (2) mutual recognition and binding of different kinds of CAM molecules on two adjacent cell surfaces (anisotropy adhesion); (3) the same CAM molecules on the surface of two adjacent cells recognize and bind each other by extracellular ligation molecules.

Biological Function

Stem cell adhesion molecules are essential for stem cell adhesion, which is a prerequisite for stem cell self-renewal. In many cases, the importance of adhesion molecules in stem cell-niche physical interaction has simply been inferred based on their expression patterns and their requirement for stem cell maintenance. If the stem cell-niche interaction mediated by particular adhesion molecules is essential for stem cell anchorage, for example, its inactivation should result in rapid stem cell departure from the niche. Cadherin molecules are also expressed in a variety of mammalian stem cells, where they similarly appear to play important roles in regulating stem cell adhesion and self-renewal. Stem cell self-renew is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles in the regulation of stem cell function, and it is clear that stem cell-niche adhesion is crucial for stem cell self-renewal and is dynamically regulated. There is a study highlight recent progress in understanding adhesion between stem cells and their niche and how this adhesion is regulated. In addition, some studies’ data suggests a role for E-cadherin in regulating correct plasma membrane localization of a range of proteoglycans in stem cells. Therefore, as well as its role in maintaining epithelial integrity, E-cadherin mediated cell-cell contact is critical for the correct presentation of a range of molecules at the cell surface of stem cells.

We all know that stem cells are pluripotent and can differentiate into a variety of cells, and the pluripotency of stem cells depends on these adhesion molecules. During embryonic development, pluripotency is progressively lost when cells proceed towards terminal differentiation. This is illustrated by Waddington’s epigenetic landscape, in which he compared the differentiation process of a cell with a marble rolling downhill along certain paths (lineage commitment), finally stopping at the bottom of the valley (terminal differentiation). However, plasticity is a common feature in biology, and primed epiblast-like stem cells can be revered to the naïve state of stem cells by exposure to LIF-STAT3 signaling, especially when also cultured in the presence of 2i or during the transient expression of pluripotency factors such as KLF4 or MYC. E-cadherin plays a dual role in determining stem cell fate and differentiation. Previous studies found that lack E-cadherin cannot form organized structures within teratomas, indicating a crucial role for E-cadherin in tissue organization during in vivo differentiation. Rigorously speaking, there are still many problems in the specific role of adhesion molecules in stem cell differentiation, but it is certain that the process of differentiation is the process of accepting cells by adhesion molecules to guide the internal cascade signals and complete the direction of differentiation.

Research Progress in Tumors at this Stage

The decrease in the expression of certain adhesion molecules on tumor stem cells can weaken the adhesion between cells, and the adhesion of tumor invasion and metastasis. At the same time, certain adhesion molecules expressed by tumor stem cells allow tumor cells that have entered the blood to adhere to vascular endothelial cells, causing distant metastasis. In addition, the effect of adhesion molecules on killing tumor cells by killer cells is reflected in two aspects: it can not only enhance the sensitivity of tumor stem cells to killer cells, but also inhibit the killing effect of killer cells on tumor cells in some cases. Tumor growth and metastasis are also closely related to local tumor thrombosis. Patients with malignant tumors often exhibit abnormalities in various coagulation and fibrinolysis indicators. Studies have shown that adhesion molecules may paly a regulatory role in the interaction of platelets, tumor cells, white blood cells and endothelial cells.

References:

  1. Abdal Dayem Ahmed, Lee Soobin, Y Choi Hye et al. The Impact of Adhesion Molecules on the In Vitro Culture and Differentiation of Stem Cells. Biotechnol J. 2018, 13(2).
  2. Polisetti Naresh, Zenkel Matthias, Menzel-Severing Johannes et al. Cell Adhesion Molecules and Stem Cell-Niche-Interactions in the Limbal Stem Cell Niche. Stem Cells. 2016, 34(1): 203-19.
  3. Park Kyoung Ho, Yeo Sang Won, Troy Frederic A. Expression of polysialylated neural cell adhesion molecules on adult stem cells after neuronal differentiation of inner ear spiral ganglion neurons. Biochem. Biophys. Res. Commun. 2014, 453(2): 282-7.
  4. Kim Won-Tae, Seo Choi Hong, Min Lee Hyun et al. B-cell receptor-associated protein 31 regulates human embryonic stem cell adhesion, stemness, and survival via control of epithelial cell adhesion molecule. Stem Cells, 2014, 32(10): 2626-41.
  5. Pieters Tim, van Roy Frans. Role of cell-cell adhesion complexes in embryonic stem cell biology. J. Cell. Sci., 2014, 127(Pt 12): 2603-13.
  6. Benvenuto Federica, Voci Adriana, Carminati Enrico et al. Human mesenchymal stem cells target adhesion molecules and receptors involved in T cell extravasation. Stem Cell Res Ther, 2015, 6: 245.
  7. Chen Shuyi, Lewallen Michelle, Xie Ting. Adhesion in the stem cell niche: biological roles and regulation. Development, 2013, 140(2): 255-65
  8. Francesca Soncin, Christopher M. Ward. The Function of E-Cadherin in Stem Cell Pluripotency and Self-Renewal. Genes, 2011, 2, 229-259.
  9. Shigdar Sarah, Lin Jia, Yu Yan et al. RNA aptamer against a cancer stem cell marker epithelial cell adhesion molecule. Cancer Sci., 2011, 102(5): 991-998
  10. de Rooij Dirk G, Repping S, van Pelt Ans M M. Role for adhesion molecules in the spermatogonial stem cell niche. Cell Stem Cell. 2008, 3(5): 467-8.
  11. Kronenwett R, Martin S, Haas R. The role of cytokines and adhesion molecules for mobilization of peripheral blood stem cells. Stem Cells. 2000, 18(5): 320-30.
  12. Ooi A G Lisa, Karsunky Holger, Majeti Ravindra et al. The adhesion molecule esam1 is a novel hematopoietic stem cell marker. Stem Cells. 2009, 27(3): 653-61.
  13. Ng Valerie Y, Ang Sheu Ngo, Chan Jia Xin et al. Characterization of epithelial cell adhesion molecule as a surface marker on undifferentiated human embryonic stem cells. Stem Cells. 2010, 28(1): 29-35.
  14. Ourednik Václav, Ourednik Jitka, Xu Yifang et al. Cross-talk between stem cells and the dysfunctional brain is facilitated by manipulating the niche: evidence from an adhesion molecule. Stem Cells. 2009, 27(11): 2846-56.

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