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## IntechOpen Book Series Physiology Volume 8

Dr Lasfar is a full member of the Cancer Institute of New Jersey and a Professor at Rutgers University, New Jersey. He is also editor and board member of several international journals and books. Dr Lasfar is a scientific adviser to the pharmaceutical industry and a member of several medical and scientific societies. He is also Head of the Cancer Immunotherapy Laboratory at Rutgers University, funded by the National Cancer Institute. Dr

Lasfar graduated in Medical and Applied Science from Paris Rene Descartes University in France. He completed his doctoral studies in Immunology at Paris Diderot University and his postdoctoral training in Cancer Immunology at Robert Wood Johnson Medical, New Jersey

Dr Karine Cohen-Solal graduated from Paris University, France, and has extensive basic and translational research experience in melanoma and cancer metastasis. Dr Cohen-Solal is an expert in receptor-based dysregulated cellular pathways and drug resistance in oncology. Dr Cohen-Solal has received several awards including a Research Scholar Grant from the American Cancer Society, and awards from the New Jersey Commission on Cancer

Research and the Melanoma Research Foundation. Currently Dr Cohen-Solal is the Chief Scientific Officer of Lambda Pharmaceutical, an adjunct faculty member at Ernest Mario School of Pharmacy, Rutgers University.

### **Editor of Volume 8:**

**Ahmed Lasfar** Ernest Mario School of Pharmacy, Piscataway, New Jersey

#### **Karine A Cohen-Solal**

Ernest Mario School of Pharmacy, Rutgers University, Piscataway, New Jersey

**Book Series Editor: Angel Catala** National University of La Plata, Argentina

### Scope of the Series

Contents

**Section 1**

in Most Human Cancers

Promoter or Protection?

 **Section 2**

*by Hülya Yazici and Beyza Akin*

Risk Factors for Ovarian Cancer

*by Rocío Alejandra Ruiz-Manzano,* 

*by Marliyya S. Zayyan*

and Breast Cancer

*Jorge Morales-Montor*

*by Guang-Jer Wu*

**Preface III**

Mechanisms of Tumor Progression and Metastasis **1**

**Chapter 1 3**

**Chapter 2 33**

**Chapter 3 51**

Tumorigenesis Risk Factors and Role of Neuroimmune Regulations **73**

**Chapter 4 75**

**Chapter 5 103**

**Chapter 6 113**

METCAM/MUC18 Promotes Tumor Progression and Metastasis

Protein Tyrosine Phosphatases in Tumor Progression and Metastasis:

*Alessandra V. Sousa Faria, Patrícia Fernandes de Souza Oliveira,* 

Appendiceal Neuroendocrine Tumors and Anorectal Melanoma *by Marco Clementi, Renato Pietroletti, Andrea Ciarrocchi, Federica d'Ascanio, Guido Rindi and Francesco Carlei*

Neuroimmunoendocrine Interactions in Tumorigenesis

*Tania de Lourdes Ochoa-Mercado, Mariana Segovia-Mendoza, Karen Elizabeth Nava-Castro, Margarita Isabel Palacios-Arreola and* 

Molecular Genetics of Metastatic Breast Cancer

*by Carmen V. Ferreira-Halder, Stefano Piatto Clerici,* 

*Helon Guimarães Cordeiro and Erica Akagi*

Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the expression, structure, and function of molecular and cellular components. While a daunting task, learning is facilitated by our identification of common, effective signaling pathways employed by nature to sustain life. As a main example, the cellular interplay between intracellular Ca2 increases and changes in plasma membrane potential is integral to coordinating blood flow, governing the exocytosis of neurotransmitters and modulating genetic expression. Further, in this manner, understanding the systemic interplay between the cardiovascular and nervous systems has now become more important than ever as human populations age and mechanisms of cellular oxidative signaling are utilized for sustaining life. Altogether, physiological research enables our identification of clear and precise points of transition from health to development of multi-morbidity during the inevitable aging process (e.g., diabetes, hypertension, chronic kidney disease, heart failure, age-related macular degeneration; cancer). With consideration of all organ systems (e.g., brain, heart, lung, liver; gut, kidney, eye) and the interactions thereof, this Physiology Series will address aims of resolve (1) Aging physiology and progress of chronic diseases (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling & (3) how changes in plasma membrane produced by lipid peroxidation products affects aging physiology.

### Contents



Preface

Tumor metastasis results from the spreading of a primary tumor and establishment of secondary tumors, mostly in vital organs such as the lung, liver, and brain. Tumor metastasis is responsible for the majority of cancer deaths, yet it remains the

Metastatic tumor cells acquire new biological features allowing them to migrate, invade normal tissues, escape the immune system control, and develop drug resistance. Many mechanisms have been shown to play an important role in the metastatic process, particularly through the tumor microenvironment. Many factors present in the tumor microenvironment have been identified and demonstrated to play either a pro- or anti-metastatic role, allowing the development

However, despite an armamentarium of treatments, patients remain at a high risk for metastasis. Better understanding of the mechanisms leading to cancer metastasis is crucial for the development of novel and more efficacious therapies.

markers and therapeutic targets. Modern approaches including genomics, molecular biology, immunology, imaging and computational biology, are carried out in cancer research, leading to the development of novel therapeutic options. Many therapeutic options based on the manipulation or modulation of the immune system have shown unprecedented results and have provided new hope to cancer patients. The introduction of targeted and immune-based therapies have significantly improved the cancer survival rate. In addition to discussing relevant options of cancer treatment and ongoing clinical trials, recent breakthroughs in

Important efforts and collaborations with leading experts in cancer research and clinics were crucial for achieving this high quality book. We thank all the contributors for sharing their expertise, discoveries, and their views and bringing new hopes for cancer patients and their families. The readers will appreciate the

Although the cancer survival rate has significantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs (predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) also have effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, and settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion, and adhesion. These four essential metastatic steps are inter-related and affected by multi-biochemical

cancer development and metastasis are provided in this book.

excellent and reliable knowledge in this book.

Currently many research areas are involved in the identification of novel biological

least understood stage of cancer.

of new targeted therapies.
