Preface

**Section 2 Circulating Tumor Cells 143**

**VI** Contents

**Clinical Applications 145**

**Section 3 Epithelial–Mesenchymal Transition 215**

**Metastasis 217**

Chapter 8 **The Selection Strategy for Circulating Tumor Cells (CTCs)**

Jason Chia‐Hsun Hsieh and Tyler Ming‐Hsien Wu

Chapter 9 **Detection of Circulating Tumor Cells and Circulating Tumor**

Chapter 10 **Epithelial-Mesenchymal Transition and its Regulation in Tumor**

Yanjie Hu, Jin'e Zheng and Shiang Huang

Tao Sun, Yuan Qin and Wei-long Zhong

Chapter 11 **Importance and Detection of Epithelial-to-Mesenchymal Transition (EMT) Phenotype in CTCs 241**

**Isolation and Enumeration: Technical Features, Methods, and**

**Stem Cells in Breast Cancer by Using Flow Cytometry 195**

Joseph W. Po, David Lynch, Paul de Souza and Therese M. Becker

Cancer is a leading cause of death nowadays; it causes more deaths than coronary heart dis‐ ease. According to the latest report of the International Agency for Research on Cancer, there were estimated 14.1 million new cancer cases and 8.2 million deaths occurred in 2012 worldwide. Among all types of cancer, lung cancer remains the leading cause of cancer-re‐ lated death in men, and breast cancer is the leading cause of cancer-related death in women. Although governments over the world have invested huge human and material resources on cancer prevention and cancer treatment, there are no significant improvements on it. The occurrence of cancer is still increasing. This is because of the increasing risk factors such as pollution due to urbanization and economic development, aging and growth of the popula‐ tion, overweight/obesity, and the lifestyle behaviors such as smoking, physical inactivity, and poor diet.

Cancer metastasis is the major cause of cancer-related death; around 90% of cancer patients die of metastasis. Tumor metastasis is a complex process; the cascade of metastasis involves several steps: loss of cellular adhesion, increased ability of migration and invasion, entry blood and lymph vessels, exit from the circulation into new site, and colonization at the dis‐ tant site. This book provides broad coverage of the field of tumor metastasis.

In the first section of this book, "Tumor Metastasis," **Chapter 1** discusses the role of hemo‐ static system in tumor. Cancer induces hemostatic imbalance through the production and secretion of procoagulant substances, suppression of anticoagulant mechanisms, endothelial activation, and angiogenic switch. By manipulating hemostatic processes, tumor induces tol‐ erant host environment necessary for the evasion of defense attacks, survival, and progres‐ sion. **Chapter 2** reviews the role of the extracellular matrix (ECM) and how disruption of ECM dynamics may contribute to cancer. This focuses on the properties and functions of the ECM, abnormal ECM dynamics, tumor microenvironment and ECM, and the role of ECM and ECM-associated proteins in metastasis. Ovarian cancer is the most lethal of all gyneco‐ logic malignancies. Seventy percent of ovarian cancer patients present with disseminated disease at the time of diagnosis. **Chapter 3** provides an overview of ovarian cancer metasta‐ sis highlighting the unique dissemination and the underlying mechanisms of regulation of the steps involved. The role of the microenvironment in the process of metastasis is also re‐ viewed. **Chapter 4** highlights current data on the involvement of aquaporins (AQPs) in processes associated with malignant progression and discusses possible applications of AQP-based therapy as an effective means of inhibiting cancer cells from metastasis. In **Chapter 5** Soraj et al. discuss the current state of research on characterization of extracellular vesicles (EVs) and highlight possible strategies for their use in cancer therapy. In **Chapter 6**, Al-Taee et al. investigate the modulated gene expression of PDAC cells during liver coloni‐ zation. Their results show that many genes and miRNAs are modulated significantly in ex‐ pression during the early stage of liver colonization and continuously thereafter. These overall changes lead to distinguish certain categories and processes participating in cancer progression. **Chapter 7** reviews various methods of minimally invasive surgery for meta‐ static bone tumor and emphasizes on the PMMA bone cement injection technique. It also discusses optimal customized surgical options according to patient's circumstances.

Circulating tumor cells (CTCs) are defined as tumor cells which are detached from a pri‐ mary tumor or metastasis into vasculature and can be detected in the bloodstream of cancer patients. In the tumor metastasis process, CTCs play a very important role; therefore, the study of CTCs is becoming crucial in cancer management. The next section of this book is "Circulating Tumor Cells." **Chapter 8** by Hsieh et al. introduces the role of circulating tumor cells in cancer progression and the strategies for CTC isolation and enumeration. It also re‐ views the clinical applications and important findings in clinical trials. In **Chapter 9**, Hu et al. demonstrate the value of multiparameter flow cytometry in detecting breast cancer cells in the peripheral blood, which has higher sensitivity and higher specificity compared with RT-PCR. They also find that CTC number is related to TNM stage, metastasis, and the over‐ all survival of patients.

In the last section on "Epithelial-Mesenchymal Transition," **Chapter 10** introduces the key role of epithelial-mesenchymal transition (EMT) in cancer and discusses different elements of EMT cascades that could be targeted and also the difficulties in translating the preclinical findings in routine clinic. **Chapter 11** explores the significance of EMT in CTC formation and the role of EMT in cancer metastasis and resistance to therapy. It also reviews the past and current limitations of evaluating EMT phenotypes in CTC isolation and analysis.

We hope that the reviews and studies described here will provide a wide-ranging forum in the tumor metastasis field. Although significant progresses are made in tumor metastasis study, the mechanism of metastasis is still not fully understood. It is believed that based on novel achievements in metastasis study, more tumor patients will benefit from the new strategies on metastasis diagnosis and treatment, in particular the targeted therapy.

> **Ke Xu** Tianjin Lung Cancer Institute Tianjin Medical University General Hospital Tianjin, China

**Section 1**

**Tumor Metastasis**

pression during the early stage of liver colonization and continuously thereafter. These overall changes lead to distinguish certain categories and processes participating in cancer progression. **Chapter 7** reviews various methods of minimally invasive surgery for meta‐ static bone tumor and emphasizes on the PMMA bone cement injection technique. It also

Circulating tumor cells (CTCs) are defined as tumor cells which are detached from a pri‐ mary tumor or metastasis into vasculature and can be detected in the bloodstream of cancer patients. In the tumor metastasis process, CTCs play a very important role; therefore, the study of CTCs is becoming crucial in cancer management. The next section of this book is "Circulating Tumor Cells." **Chapter 8** by Hsieh et al. introduces the role of circulating tumor cells in cancer progression and the strategies for CTC isolation and enumeration. It also re‐ views the clinical applications and important findings in clinical trials. In **Chapter 9**, Hu et al. demonstrate the value of multiparameter flow cytometry in detecting breast cancer cells in the peripheral blood, which has higher sensitivity and higher specificity compared with RT-PCR. They also find that CTC number is related to TNM stage, metastasis, and the over‐

In the last section on "Epithelial-Mesenchymal Transition," **Chapter 10** introduces the key role of epithelial-mesenchymal transition (EMT) in cancer and discusses different elements of EMT cascades that could be targeted and also the difficulties in translating the preclinical findings in routine clinic. **Chapter 11** explores the significance of EMT in CTC formation and the role of EMT in cancer metastasis and resistance to therapy. It also reviews the past and

We hope that the reviews and studies described here will provide a wide-ranging forum in the tumor metastasis field. Although significant progresses are made in tumor metastasis study, the mechanism of metastasis is still not fully understood. It is believed that based on novel achievements in metastasis study, more tumor patients will benefit from the new

**Ke Xu**

Tianjin, China

Tianjin Lung Cancer Institute

Tianjin Medical University General Hospital

current limitations of evaluating EMT phenotypes in CTC isolation and analysis.

strategies on metastasis diagnosis and treatment, in particular the targeted therapy.

discusses optimal customized surgical options according to patient's circumstances.

all survival of patients.

VIII Preface
