Tumor Microenvironment: Signaling Pathways – Part A (Advances in Experimental Medicine and Biology, 1223)

Preface
Contents
Contributors
1: Shaping of the Tumor Microenvironment by Notch Signaling
	1.1	 Introduction
	1.2	 Notch Receptors and Ligands in the TME
	1.3	 Regulation of Notch Ligands and Receptors in the TME
	1.4	 Notch-Mediated Regulation of the Tumor Vasculature
		1.4.1	 Regulation of the Tip/Stalk Ratio
		1.4.2	 Regulation of the Vasculature through Ligands Expressed by the Tumor
		1.4.3	 Regulation of Notch Signaling in the Tumor Compartment by EC-Derived Ligands
	1.5	 Notch-Mediated Regulation of Cancer-Associated Fibroblasts
	1.6	 Notch Signaling in the Stem Cell Niche
	1.7	 Notch-Mediated Shaping of the Metastatic Niche
	1.8	 Notch-Mediated Shaping of the Tumor Immunity
	1.9	 Can we Predict the Effect of Notch Inhibition in the TME?
	1.10	 Open Questions and New Avenues
		1.10.1	 Notch Regulation in the Physical and Chemical Tumor Environment
		1.10.2	 Improving the Study of Notch Signaling in the TME
		1.10.3	 Specific Targeting of Notch in the TME
	1.11	 Conclusion
	References
2: Erythropoietin Signaling in the Microenvironment of Tumors and Healthy Tissues
	2.1	 Introduction
		2.1.1	 EPO and the EPO Receptor
	2.2	 Erythropoietin and Stem Cell Factor
	2.3	 Erythropoietin: Role in Proliferation and Migration in Various Cancer Types
		2.3.1	 Breast Cancer
		2.3.2	 Ovarian Cancer
		2.3.3	 Lung Cancer
		2.3.4	 Cervical Cancer
		2.3.5	 Leukemia
	2.4	 Clinical Significance of Erythropoietin Signaling
	2.5	 Concluding Remarks
	References
3: Neuropilin: Handyman and Power Broker in the Tumor Microenvironment
	3.1	 Introduction
	3.2	 Molecular Structure of Neuropilins
	3.3	 Neuropilin Signaling
		3.3.1	 Neuropilins Associate with Other Receptors into Functional Holoreceptors
		3.3.2	 Ligands of Neuropilin-Containing Signaling Complexes
		3.3.3	 Signaling of Neuropilin-Containing Complexes
		3.3.4	 NRP-Triggered Signaling Pathways
		3.3.5	 Regulation of NRPs at the Posttranscriptional Level
	3.4	 Neuropilins on Cells of the Tumor Microenvironment
		3.4.1	 Neuropilins on Tumor Cells
		3.4.2	 Neuropilins on Resident Tumor Stroma Cells
		3.4.3	 Neuropilins on Infiltrating Angiogenic Tumor Vessels
		3.4.4	 Neuropilins on Immune Cells Within the Tumor Microenvironment
	3.5	 Targeting Neuropilins for Pharmacological Intervention in the Tumor Microenvironment
	References
4: Translational Landscape of mTOR Signaling in Integrating Cues Between Cancer and Tumor Microenvironment
	4.1	 Introduction
	4.2	 mTOR in TME Elements
	4.3	 Implication of mTOR Signaling in Angiogenesis and Immunotherapy
	4.4	 Commentary
	References
5: Toll-Like Receptors Signaling in the Tumor Microenvironment
	5.1	 Introduction
	5.2	 Inflammation and Cancer
	5.3	 Antitumor Immune Responses
	5.4	 Tumor-Promoting Immune Responses
	5.5	 Pattern Recognition Receptors
	5.6	 Toll-Like Receptors
	5.7	 dsRNA-Activated Receptors
	5.8	 TLR Signaling in the Tumor Microenvironment Contributes to Antitumor Immune Responses
	5.9	 TLR Signaling in Tumor Cells: Negative Consequences
	5.10	 Future Trends and Directions
	References
6: Rho-ROCK Signaling in Normal Physiology and as a Key Player in Shaping the Tumor Microenvironment
	6.1	 Introduction
		6.1.1	 Core Components of the Rho-ROCK Pathway
		6.1.2	 Key Functions Regulated by Rho-ROCK Signaling
		6.1.3	 Regulation of the Rho-ROCK Pathway
	6.2	 Rho-ROCK Signaling in Development
		6.2.1	 Importance of the Rho-ROCK Pathway for the Earliest Stages of Development
		6.2.2	 The Role of Rho-ROCK in Germ Layer Establishment and Maintenance
		6.2.3	 Requirement of Rho-ROCK for Migration During Development
		6.2.4	 Rho-ROCK Signaling Has Key Roles During Tissue Formation
		6.2.5	 Rho-ROCK Pathway in Organ Formation
	6.3	 Rho-ROCK Signaling in Normal Physiology and Adult Tissue Homeostasis
		6.3.1	 Homeostasis
		6.3.2	 Immunity
		6.3.3	 Glucose Transport and Voltage Channel Trafficking
	6.4	 Deregulation of Rho-ROCK Signaling in Disease
		6.4.1	 The Role of Rho-ROCK Signaling in Promoting Cancer Initiation and Progression
		6.4.2	 What Is the Tumor Microenvironment and What Is Its Role in Promoting Cancer Progression?
		6.4.3	 Roles of Rho-ROCK Signaling in the TME
			6.4.3.1	 Rho-ROCK Regulation of CAFs in the TME
			6.4.3.2	 Rho-ROCK Regulation of the ECM in the TME
			6.4.3.3	 Rho-ROCK Regulation of Immune Cells in the TME
			6.4.3.4	 Rho-ROCK Dynamics in the TME of Pancreatic Cancer: Implications for Therapeutic Targeting
			6.4.3.5	 The Rho-ROCK Pathway Functions in the TME of Breast Cancer and Represents a Potential Therapeutic Target
			6.4.3.6	 Rho-ROCK Signaling in the TME of Renal Cancer
			6.4.3.7	 Rho-ROCK Signaling in the TME of Urothelial Cancers
			6.4.3.8	 The Rho-ROCK Pathway in Osteosarcoma
	6.5	 Targeting Rho-ROCK Signaling in the Cancer TME
		6.5.1	 Targeting Rho-ROCK Signaling in the Cancer TME of PDAC
	6.6	 Conclusions, Future Trends, and Directions
	References
7: S1P Signaling in the Tumor Microenvironment
	7.1	 Introduction
	7.2	 Metabolism of S1P
	7.3	 Sources of S1P in TME
	7.4	 S1P Signaling
	7.5	 S1P as a Modulator of Cancer Biology
	7.6	 S1P as a Modulator of the Immune Response
	7.7	 S1P as a Modulator in Inflammatory Pathways
	7.8	 S1P as a Regulator of Cells’ Interaction
	7.9	 S1P and Hypoxia
	7.10	 S1P-Targeting Anticancer Therapies
	7.11	 Conclusions
	References
8: CD200-CD200R Pathway in the Regulation of Tumor Immune Microenvironment and Immunotherapy
	8.1	 Introduction
	8.2	 The Biology of CD200-CD200R Axis
	8.3	 CD200-CD200R Interaction in Tumor Microenvironment and its Impact on Tumor Growth and Progression
	8.4	 CD200-CD200R Interaction in Regulating Activation and Effector Functions of Tumor-Specific T Cells
	8.5	 Is Targeting CD200-CD200R Feasible for Cancer Immunotherapy?
	8.6	 Concluding Remarks and Future Perspective
	References
Index