SPECIAL ISSUE - CD44, PREFACE

	[Frontiers in Bioscience 3, July 1, 1998]
	SPECIAL ISSUE - CD44, ITS SIGNIFICANCE FOR TUMOR PROGRESSION AND METASTASIS Managing Editor: Lloyd A. Culp Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106 PREFACE CD44 is a complex transmembrane protein at the surface of many cell types in higher organisms. Its plasma membrane-external region codes for sequences that bind hyaluronan and function for lymphocyte homing at regions of inflammation. Its cytoplasmic domain harbors sequences that bind to the cytoskeleton. CD44 is also marked by a complex pattern of alternative splicing, all of which occurs in membrane-external sequences. There is mounting evidence that specific CD44 isoforms also bind to ligands that have yet to be identified. This special edition of the Frontiers in Bioscience brings together many reviews from prominent investigators in this field of cell and tumor biology to offer a more concerted summary of the structure and functions of CD44 as they apply to the progression and metastasis of various tumor classes in humans and in animal model systems. A variety of topic areas are covered in these reviews. These include some basic information from all systems on the complexity of the structure and function of CD44 isoforms (by Lesley and Hyman). Also, two reviews focus specifically on CD44 binding to hyaluronan (by Knudson and by Sy and his collaborators). Review is provided for CD44 "association" with the cytoskeleton of the cell (by Bourguignon and her collaborators). Goodison and Tarin focus on analyses of human tumor material directly to define isoform significance in human disease. Similarly, Ponta and Herrlich bring together their studies with isoform expression in various human cancers with parallel studies in animal model systems. One review centers of the relationship between growth factor activity in cells and CD44 expression (by Hamada and his collaborators). Rafi-Janajreh and colleagues describe the role of CD44 in CTL and NK cell activity. Finally, our own laboratory reviews evidence for the remarkable plasticity of expression of CD44 during progression and metastasis in an animal model system, as well as the mechanism of that plasticity (by Culp and Kogerman). All of this evidence is becoming compelling for the significance of CD44 expression during specific stages of cancer progression and metastasis, but only in some human malignancies. CD44 "variant" isoforms appear to be highly important in carcinoma progression while CD44 "standard" isoform applies specifically to lymphoma and fibrosarcoma progression. Therefore, there is considerable cell-type and tumor-type specificity for the functions of this family of molecules. Whether this molecule can become the focus of clinical intervention remains to be seen. The evidence provided in this special edition provides considerable optimism that in the near future we will have greater understanding of how this molecule operates in some human cancers and mechanisms for altering its regulation to the betterment of the patient.

[Frontiers in Bioscience 3, July 1, 1998]

SPECIAL ISSUE - CD44, ITS SIGNIFICANCE FOR TUMOR PROGRESSION AND METASTASIS

Managing Editor: Lloyd A. Culp

Department of Molecular Biology and Microbiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106

PREFACE

CD44 is a complex transmembrane protein at the surface of many cell types in higher organisms. Its plasma membrane-external region codes for sequences that bind hyaluronan and function for lymphocyte homing at regions of inflammation. Its cytoplasmic domain harbors sequences that bind to the cytoskeleton. CD44 is also marked by a complex pattern of alternative splicing, all of which occurs in membrane-external sequences. There is mounting evidence that specific CD44 isoforms also bind to ligands that have yet to be identified. This special edition of the Frontiers in Bioscience brings together many reviews from prominent investigators in this field of cell and tumor biology to offer a more concerted summary of the structure and functions of CD44 as they apply to the progression and metastasis of various tumor classes in humans and in animal model systems.

A variety of topic areas are covered in these reviews. These include some basic information from all systems on the complexity of the structure and function of CD44 isoforms (by Lesley and Hyman). Also, two reviews focus specifically on CD44 binding to hyaluronan (by Knudson and by Sy and his collaborators). Review is provided for CD44 "association" with the cytoskeleton of the cell (by Bourguignon and her collaborators). Goodison and Tarin focus on analyses of human tumor material directly to define isoform significance in human disease. Similarly, Ponta and Herrlich bring together their studies with isoform expression in various human cancers with parallel studies in animal model systems. One review centers of the relationship between growth factor activity in cells and CD44 expression (by Hamada and his collaborators). Rafi-Janajreh and colleagues describe the role of CD44 in CTL and NK cell activity. Finally, our own laboratory reviews evidence for the remarkable plasticity of expression of CD44 during progression and metastasis in an animal model system, as well as the mechanism of that plasticity (by Culp and Kogerman).

All of this evidence is becoming compelling for the significance of CD44 expression during specific stages of cancer progression and metastasis, but only in some human malignancies. CD44 "variant" isoforms appear to be highly important in carcinoma progression while CD44 "standard" isoform applies specifically to lymphoma and fibrosarcoma progression. Therefore, there is considerable cell-type and tumor-type specificity for the functions of this family of molecules. Whether this molecule can become the focus of clinical intervention remains to be seen. The evidence provided in this special edition provides considerable optimism that in the near future we will have greater understanding of how this molecule operates in some human cancers and mechanisms for altering its regulation to the betterment of the patient.