L.A. Liotta – författare

The success rate for treatment of primary neoplasms has improved sig­ nificantly due to improved surgical, radiotherapy, and chemotherapy methods, and by supportive patient care. In contrast, the treatment of cancer metastases, the cause of most cancer deaths, has not been very successful. Approximately 50% or more of patients with primary malignant neoplasms already have established metastases. Consequently, the most important problem in cancer treatment is the destruction or prevention of metastases. Metastases research has obvious clinical importance. Yet it has only been recently that investigators have attempted to study the mechanisms in­ volved in this process. This is in part due to the complexity of metastases formation. A metastatic colony is the result of a complicated series of steps involving mUltiple tumor host interactions. It is expected that multiple biochemical factors and gene products derived both from the host and the tumor cell may be required for the metastasizing tumor cell to invade, survive host defenses, travel in the circulation, arrest and adhere in the target organ, invade out, and grow as a metastatic colony. Some of these factors have recently been identified by investigators who have focused on individual steps in the metastatic process and have employed new technologies in immunology, biochemistry and molecular biology. The purpose of this volume is to capture some of the excitement in the field of metastases based on such new discoveries.

Recent experimental evidence has made it increasingly clear In particular, this volume reviews the discrete steps involved that the properties of invasive, malignant cells during tumor in metastatic invasion: the interaction of invasive tumor cells development substantially impact on the host. This is under­ with extracellular matrices, the basement membrane, attach­ scored by a variety of biochemical properties of tumor cells ment to extracellular matrices, local proteolytic degradation during their differentiation and metastatic dissemination. of matrices, and the locomotion of invasive tumor cells These properties can be analyzed at different stages of tumor through such areas of localized degradation. The critical growth and progression and this volume explores the role of the cell surface in secondary tumor formation is characteristics of primary tumors as well as the shared reviewed as are important advances in the molecular biology characteristics of both primary and secondary tumors. of metastasis initiation and maintenance. Recent advances The primary tumor comes into existence following in the role of DNA methylation in the generation of tumor preneoplastic biochemical and cellular events that ultimate­ cell heterogeneity and tumor progression are also critically ly result in malignant transformation. Various aspects of summarized. Chapters in this volume also review molecular metabolism, predetermined by nutritional status, often play aspects of metastatic progression, and the use of the tech­ a basic role. Obesity, for example, is cancer-promoting. Cell nologies of DNA transfection and somatic cell fusion in the surface carbohydrates, cytoskeletal proteins, glycoproteins, exploration of molecular aspects of metastatic progression.

The success rate for treatment of primary neoplasms has improved sig­ nificantly due to improved surgical, radiotherapy, and chemotherapy methods, and by supportive patient care. In contrast, the treatment of cancer metastases, the cause of most cancer deaths, has not been very successful. Approximately 50% or more of patients with primary malignant neoplasms already have established metastases. Consequently, the most important problem in cancer treatment is the destruction or prevention of metastases. Metastases research has obvious clinical importance. Yet it has only been recently that investigators have attempted to study the mechanisms in­ volved in this process. This is in part due to the complexity of metastases formation. A metastatic colony is the result of a complicated series of steps involving mUltiple tumor host interactions. It is expected that multiple biochemical factors and gene products derived both from the host and the tumor cell may be required for the metastasizing tumor cell to invade, survive host defenses, travel in the circulation, arrest and adhere in the target organ, invade out, and grow as a metastatic colony. Some of these factors have recently been identified by investigators who have focused on individual steps in the metastatic process and have employed new technologies in immunology, biochemistry and molecular biology. The purpose of this volume is to capture some of the excitement in the field of metastases based on such new discoveries.

The success rate for treatment of primary neoplasms has improved sig­ nificantly due to improved surgical, radiotherapy, and chemotherapy methods, and by supportive patient care. In contrast, the treatment of cancer metastases, the cause of most cancer deaths, has not been very successful. Approximately 50% or more of patients with primary malignant neoplasms already have established metastases. Consequently, the most important problem in cancer treatment is the destruction or prevention of metastases. Metastases research has obvious clinical importance. Yet it has only been recently that investigators have attempted to study the mechanisms in­ volved in this process. This is in part due to the complexity of metastases formation. A metastatic colony is the result of a complicated series of steps involving mUltiple tumor host interactions. It is expected that multiple biochemical factors and gene products derived both from the host and the tumor cell may be required for the metastasizing tumor cell to invade, survive host defenses, travel in the circulation, arrest and adhere in the target organ, invade out, and grow as a metastatic colony. Some of these factors have recently been identified by investigators who have focused on individual steps in the metastatic process and have employed new technologies in immunology, biochemistry and molecular biology. The purpose of this volume is to capture some of the excitement in the field of metastases based on such new discoveries.

The pUrpOSE! of this conference was not to define the two areas that are being bound, which might be a well nigh impossible proposition. Rather, its focus was to concentrate on the mechanistic similarities between promotion and progression. Are the areas involved within the boundaries a continuum? Are these two simultaneous processes? Or are some of the affected cells in the stage of promotion when at the same time others have undergone irreversi­ ble changes tha. t position them in the stage of progression? Or are these two stages the same thing, but called by different names? To explore such concepts we assembled investigators with various back­ grounds and asked them to specifically address these and other questions about "The Boundaries", within the context of the session to which they con­ tributed. The conference lasted two and a half days, from Wednesday to Friday. There were at least four speakers per session with morning and after­ noon sessions each day, except on Friday when the meeting ended at noon. The first day, each speaker had 25 minutes to present a position, followed by five minutes of discussion. At the end of the session there were 40 or 50 minutes of exchange on all the issues examined. For the remaining days, there were 25 minutes of presentation and 15 minutes of discussion.

The pUrpOSE! of this conference was not to define the two areas that are being bound, which might be a well nigh impossible proposition. Rather, its focus was to concentrate on the mechanistic similarities between promotion and progression. Are the areas involved within the boundaries a continuum? Are these two simultaneous processes? Or are some of the affected cells in the stage of promotion when at the same time others have undergone irreversi­ ble changes tha. t position them in the stage of progression? Or are these two stages the same thing, but called by different names? To explore such concepts we assembled investigators with various back­ grounds and asked them to specifically address these and other questions about "The Boundaries", within the context of the session to which they con­ tributed. The conference lasted two and a half days, from Wednesday to Friday. There were at least four speakers per session with morning and after­ noon sessions each day, except on Friday when the meeting ended at noon. The first day, each speaker had 25 minutes to present a position, followed by five minutes of discussion. At the end of the session there were 40 or 50 minutes of exchange on all the issues examined. For the remaining days, there were 25 minutes of presentation and 15 minutes of discussion.

Recent experimental evidence has made it increasingly clear In particular, this volume reviews the discrete steps involved that the properties of invasive, malignant cells during tumor in metastatic invasion: the interaction of invasive tumor cells development substantially impact on the host. This is under­ with extracellular matrices, the basement membrane, attach­ scored by a variety of biochemical properties of tumor cells ment to extracellular matrices, local proteolytic degradation during their differentiation and metastatic dissemination. of matrices, and the locomotion of invasive tumor cells These properties can be analyzed at different stages of tumor through such areas of localized degradation. The critical growth and progression and this volume explores the role of the cell surface in secondary tumor formation is characteristics of primary tumors as well as the shared reviewed as are important advances in the molecular biology characteristics of both primary and secondary tumors. of metastasis initiation and maintenance. Recent advances The primary tumor comes into existence following in the role of DNA methylation in the generation of tumor preneoplastic biochemical and cellular events that ultimate­ cell heterogeneity and tumor progression are also critically ly result in malignant transformation. Various aspects of summarized. Chapters in this volume also review molecular metabolism, predetermined by nutritional status, often play aspects of metastatic progression, and the use of the tech­ a basic role. Obesity, for example, is cancer-promoting. Cell nologies of DNA transfection and somatic cell fusion in the surface carbohydrates, cytoskeletal proteins, glycoproteins, exploration of molecular aspects of metastatic progression.

The clinical significance of tumor spread has always been appreciated. Yet, in spite of the pioneering work and outstanding contributions of investigators such as D. Coman, H. Green, B. Fisher, S. Wood and I. Zeidman, studies on metastasis rarely achieved the popularity afforded to more esoteric areas of tumor biology. Tumor dissemination, occurring as it does in a responding host and being composed of a series of dynamic int~ractions, is a highly complex phenomenon. Few investigators were brave enough to attempt to unravel the mechanisms involved. Paradoxically, this very complexity may have contributed, in part, to the recent upsurge of interest in metastasis research. More and more researchers are becoming fascinated by the complexities of the cellular interactions involved in tumor spread. Accompanying this intellectual stimulation have been technological advances in related fields which allow the derivation of new model systems. The mechanisms of metastatic spread are increasingly amenable to both the reductionist and holistic approaches and it is the purpose of this volume to present many of these model systems while emphasizing the intricacy and complexity of the processes they mimic. We have attempted to emphasize two topics not previously covered in depth in previous books on metastases. These are in vitro models of invasion and in­ teractions of tumor cells with connective tissue.