Inflammation and immunology
C. Simon Herrington in Muir's Textbook of Pathology, 2020
Obviously, the response of endothelial cells on activation adjacent to tissue injury is critical in signalling to leukocytes in the circulation. Expression of cell adhesion molecules is controlled in several different ways in these cell types. Molecules such as P-selectin are stored preformed in endothelial cells in Weibel–Palade bodies. On stimulation of the endothelial cells by histamine or platelet-activating factor (PAF), the P-selectin within these cytoplasmic storage granules is rapidly redistributed to the cell surface within minutes. Thus the expression of P-selectin on the endothelium is an important early mechanism for attracting leukocytes to a site of inflammation. Other adhesion molecules, including E-selectin, ICAM-1, and VCAM-1, are expressed by new protein synthesis. On stimulation of the endothelial cells by proinflammatory cytokines such as TNF or interleukin 1 (IL-1) there is transcriptional activation of the genes encoding these proteins. This level of control of adhesion molecules requires between 4 and 6 hours of stimulation but can be sustained for hours or days.
General Biology of Cancer and Metastasis
Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George in The Scientific Basis of Urology, 2010
Decreased intercellular adhesiveness favors detachment of tumor cells, and this may play a role in regression to metastatic disease. At least four families of cell adhesion molecules are thought to be involved in cell-cell adhesion (cadherins, selectins, immunoglobulins, and integrins). The most widely studied have been E-cadherin, a cell surface glycoprotein restricted to epithelial tissue, which is involved in calciumdependent homotypic cell-cell adhesion, and the vascular cell adhesion molecules, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). The regulation of the expression of E-cadherin on tumor cells is unclear. Posttranslational modification of the protein product may affect function. It is known that three molecules (a, b, and c catenins) form bridges between the cytoplasmic tail of E-cadherin and the cytoskeleton, a bridging that may be necessary for E-cadherin to function normally.
Chemopreventive Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Interestingly, the SNAIL signaling pathway triggers breast cancer metastasis but has no relevance in pancreatic cancer models. Also, EMT can be reversed via Mesenchymal-Epithelial Transition (MET) which is thought to facilitate the implanting of circulating tumor cells to develop secondary tumors when they reach a desirable target metastatic site. As part of this processes, the Extracellular Matrix (ECM) must be degraded, which is carried out by a proteolytic enzyme family, the Matrix Metalloproteinases (MMPs). These enzymes are key to tumor invasion, allowing tumor cells to degrade the ECM, penetrate the basement membrane, and move to other sites. MMPs also regulate cellular adhesion, which makes it easier for tumor cells to migrate. Cell Adhesion Molecules (CAMs) also play a significant role in tumor development and metastases, and include four groups: the Cadherins, Selectins, Integrins, and the Immunoglobulin Superfamily. A reduction or loss in Cadherin expression has been observed in some epithelial cancers, which is associated with increased invasion and metastasis. Activation of CAM proteins, including kinases and chemokines, can induce downstream signaling pathways, which ultimately promotes tumor growth and progression. Some chemopreventive agents are thought to work by inhibiting key regulators to suppress tumor invasion and metastasis.
Pathology of breast cancer metastasis and a view of metastasis to the brain
Published in International Journal of Neuroscience, 2023
Md Sakibuzzaman, Shahriar Mahmud, Tanzina Afroze, Sawsan Fathma, Ummul Barakat Zakia, Sabrina Afroz, Farzina Zafar, Maksuda Hossain, Amit Barua, Sabiha Akter, Hasanul Islam Chowdhury, Eram Ahsan, Shayet Hossain Eshan, Tasnuva Tarannum Fariza
The first step of metastasis is CD from the primary breast tumor. EMT allows the epithelial cells to lose cell polarity along with cell-cell adhesion and to differentiate into mesenchymal cells acquiring an increased ability to migrate, invade, and evade apoptosis [3,36–38]. However, EMT is not mandatory for breast cancer metastasis to all sites [35]. Cell adhesion molecules (CAMs) mainly consist of epithelial proteins (cadherin, selectin, and integrin). Among them, E-cadherin plays a vital role in epithelial cell adhesion [39]. Loss of E-cadherin facilitates CD. CD induces the expression of mesenchymal proteins (N-cadherin and vimentin), downregulates the expression of E-cadherin [40,41], and stimulates resistance to programmed cell death [41,42]. Thus, BCCs acquire a mesenchymal phenotype in the process of EMT. The Wnt signaling pathway regulates EMT. The knockdown of lncRNA UCA1 increases the expression of a crucial CAM, decreases the expression of mesenchymal proteins, and demotes the Wnt signaling pathway required for EMT [43]. Therefore, lncRNA UCA1 could be a therapeutic target to suppress EMT.
The claudin–transcription factor signaling pathway
Published in Tissue Barriers, 2021
The work discussed in the present review highlights the CLDN–transcription factor signaling pathway, notably the CLDN/SFK/PI3K/AKT/nuclear receptor cascade. Cell–cell and cell–matrix adhesion molecules are indispensable not only for proper tissue integrity but also for signaling properties that coordinate a wide range of cell behaviors. In other words, appropriate tissue formation connected by various cell adhesion proteins should be pre-requested for normal cell-adhesion signal. Since cell–cell and cell–matrix adhesion proteins are broadly expressed in distinct cell types, we propose that various combinations of cell adhesion molecules and transcription factors coordinate diverse physiological and pathological processes, including cancer. The cell-adhesion signals most probably lead to posttranslational modification of transcription factors, thereby regulating their activities. In future, it would be interesting to generalize the cell adhesion–transcription factor signaling pathway in health and disease.
Fusobacterium nucleatum promotes colorectal cancer cells adhesion to endothelial cells and facilitates extravasation and metastasis by inducing ALPK1/NF-κB/ICAM1 axis
Published in Gut Microbes, 2022
Ying Zhang, Lu Zhang, Sheng Zheng, Mengjie Li, Chaochao Xu, Dingjiacheng Jia, Yadong Qi, Tongyao Hou, Lan Wang, Boya Wang, Aiqing Li, Shujie Chen, Jianmin Si, Wei Zhuo
During metastasis, cancer cells leave the original tumor organ and migrate to the target metastasis organs through a process that involves intravasation, adhesion and extravasation, among which the adhesion to endothelial cells and trans-endothelial invasion of tumor cells are key steps in the metastatic process.3,4 Indeed, changes in the expression or functions of cell adhesion molecules have been implicated in all steps of tumor progression. Cell adhesion molecules belonging to the immunoglobulin superfamily commonly play critical and necessary roles in metastasis,5–7 among which intercellular adhesion molecule 1 (ICAM1) is a well-known transmembrane glycoprotein involved in cell-cell direct interactions.7 The interaction between ICAM1 and its specific ligand could facilitate the adhesion of cancer cells to the vascular endothelium and subsequently in the promotion of metastasis. Importantly, the expression of ICAM1 was positively correlated with cancer progression and metastasis.8–10
Related Knowledge Centers
- Antibody
- Cadherin
- Cytoskeleton
- Integrin
- Proteoglycan
- Extracellular Matrix
- Cell Surface Receptor
- Molecular Binding
- Membranome Database
- Immunoglobulin Superfamily