Analysis of molecular functions of the tumor metastasis promoting surface molecule CD44v4-v7 using transgenic mice.
In certain circumstances, metastatic tumor cells may mimic the molecular properties and behaviour of lymphocytes. Support for this hypothesis has come from the observation that activated lymphocytes and some tumor cells need a CD44 variant isoform (CD44v) to survive and/or expand in the lymphatic system. CD44 variant (CD44v) isoforms are created by differential splicing from a pool of at least ten variant exons (v1-v10), the encoded sequences of which are absent in the CD44 standard isoform (CD44s). To dissect the molecular interactions of CD44v, transgenic animals have been generated that constitutively express a variant of CD44 containing sequences encoded by exons v4 to v7 on the surface of T cells. Lymphocytes derived from these transgenic animals show accelerated entry into S phase upon antigenic stimulation, and a subpopulation of the cells constitutively express early lymphocyte activation markers. Our data support the hypothesis that the presence of CD44v4-v7 on the surface of T cells mediates intercellular or intracellular processes which result in the promotion of T cells towards a preactivated state.
Moll
J
J
Kernforschungszentrum Karlsruhe, Institut für Genetik, Germany.
Sleeman
J
J
Kondo
K
K
Hekele
A
A
Plug
R
R
Sherman
L
L
Ponta
H
H
Herrlich
P
P
Schmidt
A
A
Zöller
M
M
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002465:Cell Movement; D005091:Exons / Q000235:genetics; D005326:Fetal Proteins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D018960:Hyaluronan Receptors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016201:Receptors, Lymphocyte Homing / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology
D005326:Fetal Proteins; D018960:Hyaluronan Receptors; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016201:Receptors, Lymphocyte Homing; D011993:Recombinant Fusion Proteins