Laminins are a family of disulfide-linked heterotrimeric proteins consisting of 3 different subunits termed α, β, and γ chains. Combinations of 11 characterized laminin subunits (α1-α5, β1-β3, and γ1-γ3) generate at least 12 laminin isoforms, which can serve different functions. Although expression of laminin in the hematopoietic microenvironment has been known for many years, the nature of the laminin isoforms present in the human bone marrow is poorly characterized. The present study attempts to clarify this issue. Reverse transcriptase–polymerase chain reaction analysis of human bone marrow stromal cells suggested the expression of many laminin isoforms in the marrow. Northern blot and immunoblot analysis, however, showed that laminin-8/9 and laminin-10/11 are the most abundant laminin isoforms synthesized by human bone marrow stromal cells. Other isoforms, if present, certainly play a minor role in the hematopoietic microenvironment. Functionally, laminin-10/11 preparations showed strong adhesive interactions with human CD34+ cell lines. Antibodies against the β1 integrin subunit inhibited these interactions. Other laminin isoforms, especially laminin-1 and laminin-2/4, showed only weak or no adhesive interactions with the hematopoietic cell lines tested, explaining former negative results. In addition to its adhesion-mediating properties, laminin-10/11 preparations also showed a mitogenic activity for human hematopoietic progenitor cells. Taken together, these data suggest that laminin in the bone marrow plays a hitherto unexpected important function in the development of hematopoietic progenitor cells.

Renal cell carcinomas (RCCs) represent 3% of all adult malignancies and are often associated with poor prognosis due to early metastasis and limited beneficial effects of current therapeutic modalities. 1 Most of these tumors originate from the proximal tubule. According to cell morphology and growth pattern, 3 main histologic tumor types can be distinguished, including clear cell carcinoma, papillary renal carcinoma and chromophobe RCC. 2 Several factors that may contribute to the process of malignant cell transformation in RCC have previously been characterized, including physical agents, chemical agents, habits, genetics (chromosomal rearrangement) and end-stage renal disease. 3 However, the pathogenic mechanisms that promote tumor progression, i.e., tumor invasion and metastasis, still have to be defined. There is accumulating evidence that cadherins may be involved in the pathogenesis of various human carcinomas by modulating celladhesive properties.The cadherin superfamily represents a group of cell-surface glycoproteins involved in cell recognition, cell signaling, cell communication, morphogenesis as well as angiogenesis and includes the groups of classic cadherins, desmosomal cadherins, protocadherins, 7TM-cadherins and T-cadherin. 4 The human classic cadherins are a group of cell-surface molecules mediating Ca 2ϩ -dependent cell adhesion by homo-or heterophilic interaction. These proteins, m.w. approximately 120 -130 kDa, are composed of an extracellular domain with 5 subdomains, each of which contains a cadherin-specific motif at the N-terminal site, a single transmembrane domain and a rather short and highly conserved cytoplasmic domain at the C-terminal site. The adhesive action of cadherins depends on the presence of Ca 2ϩ and on the function of the intracellular domain. 5 Cadherins are linked to the actin filament network through cytoplasmic interactions with catenins. These catenins regulate cadherin-mediated cell-cell adhesion. 6 In addition, these molecules may function as a downstream transcriptional activator. 7,8 More than 12 different molecules of the classic human cadherins have been identified so far by cDNA cloning. With respect to sequence homology and conservation of several amino acid residue motifs in the extracellular domain, Suzuki et al. 9 first proposed subdividing the classic human cadherins into 2 subgroups: type I (E-, N-and P-cadherins, cadherin-4) and type II (cadherins 5-15). Cadherin-8, a type II cadherin, was cloned by Tanihara et al. 10 and is characterized by strong sequence homology with the classical type I cadherins. 11 In mice, cadherin-8 expression is restricted to the developing CNS and thymus. 12,13 As has been demonstrated for type I cadherins, type II cadherins interact with ␣-and ␤-catenins. 14 Using an L-fibroblast cDNA transfection system and a long-term cell-aggregation assay, Shimoyama et al. 15 clearly demonstrated that all 8 type II cadherins exhibited cell-cell binding activity comparable to that of E-cadherin. Heterophilic interactions among the type I...

Laminins are a family of disulfide-linked heterotrimeric proteins consisting of 3 different subunits termed α, β, and γ chains. Combinations of 11 characterized laminin subunits (α1-α5, β1-β3, and γ1-γ3) generate at least 12 laminin isoforms, which can serve different functions. Although expression of laminin in the hematopoietic microenvironment has been known for many years, the nature of the laminin isoforms present in the human bone marrow is poorly characterized. The present study attempts to clarify this issue. Reverse transcriptase–polymerase chain reaction analysis of human bone marrow stromal cells suggested the expression of many laminin isoforms in the marrow. Northern blot and immunoblot analysis, however, showed that laminin-8/9 and laminin-10/11 are the most abundant laminin isoforms synthesized by human bone marrow stromal cells. Other isoforms, if present, certainly play a minor role in the hematopoietic microenvironment. Functionally, laminin-10/11 preparations showed strong adhesive interactions with human CD34+ cell lines. Antibodies against the β1 integrin subunit inhibited these interactions. Other laminin isoforms, especially laminin-1 and laminin-2/4, showed only weak or no adhesive interactions with the hematopoietic cell lines tested, explaining former negative results. In addition to its adhesion-mediating properties, laminin-10/11 preparations also showed a mitogenic activity for human hematopoietic progenitor cells. Taken together, these data suggest that laminin in the bone marrow plays a hitherto unexpected important function in the development of hematopoietic progenitor cells.