Integrin alpha3beta1 can promote adhesion and spreading of metastatic breast carcinoma cells on the lymph node stroma.

We have reported that metastatic human melanoma cells utilize the alpha (v)beta3 integrin to adhere to lymph node vitronectin (VN). In the present study, the adhesion of human and rat breast carcinoma cells to lymph node tissue was analyzed. We have previously shown a correlation between the metastatic potential of breast carcinoma cells and an RGD-mediated adhesion to cryostat sections of peripheral lymph nodes; this adhesion could be blocked by an antibody to the integrin beta1 subunit. Here, we show that the metastatic breast carcinoma cells were significantly more adherent to fibronectin (FN) expressed by lymph node-derived stromal cells than non-metastatic cells. Metastatic cells also spread more rapidly than non-metastatic cells on FN-coated substrates. Using a combination of immunofluorescence microscopy, immunoprecipitation and blocking assays with integrin-specific antibodies, we found (i) that expression of the alpha3beta1 integrin on metastatic mammary carcinoma cells was specifically increased in comparison to non-metastatic cells and (ii) that the alpha3beta1 receptor was involved in the increased adhesion of metastatic cells to lymph node FN and in cell spreading on FN-coated substrates. Our data also suggest that the alpha5beta1 integrin, which is also expressed on the metastatic cells, did not contribute to this increase in adhesion. Our data implicate the alpha3beta1 integrin in adhesion to lymph node stromal cell FN and suggest that metastatic cells of different tissue origins (e.g., melanoma and breast carcinoma) may utilize distinct integrin-ligand combinations to colonize the same target organ.

Pefloxacin in the treatment of childhood nephrotic syndrome: a case report.

The idiopathic nephrotic syndrome (INS) of childhood is characterized chiefly by a remitting and relapsing course and its striking susceptibility to corticosteroid therapy. We report a case of relapsing nephrotic syndrome associated with urinary tract infection (UTI) treated with pefloxacin, which is a fluoro-quinolone derivative, in a dose of 800 mg per day. Steroids were avoided because of associated UTI. The UTI responded well and proteinuria disappeared after ten days of treatment with pefloxacin. However, the patient developed arthralgia involving the ankles, the knees and the neck. At this juncture, the drug was discontinued resulting in complete cessation of the joint pain. Pefloxacin increases the production of interleukin-2, a cytokine whose metabolism is modified during nephrotic syndrome. It has been used earlier in children with INS with equivocal results. The toxicity of quinolones for the joints seems more frequent in children, whose cartilage is immature and several cases have been reported. Studies on a larger number of patients are required before drawing any firm conclusions on the usefulness of pefloxacin in the treatment of INS.

[A case of joint toxicity from pefloxacin in the treatment of nephrotic syndrome in a child]. / Un cas de toxicité articulaire de la pefloxacine dans le traitement du syndrome néphrotique de l'enfant.

In order to improve the nephrotic syndrome management, we tried to treat one patient by pefloxacin. A polytenosynotis was noticed during this treatment and motivated it stopping. Remission of proteinuria was obtained after an eleven days treatment. This case give us the opportunity to discuss the possible toxicity of quinolones on joints and the efficacy of pefloxacin in this disease.

Isolation and characterization of rat lymphatic endothelial cells.

Monolayer cultures of rat lymphatic endothelial cell were obtained from explants of rat thoracic ducts. The cells displayed a typical cobblestone morphology, expressed von Willebrand factor (factor VIII-associated antigen) and angiotensin converting enzyme, and took up acetylated-low density lipoprotein, being indistinguishable by these criteria from blood vessel endothelial cells. The availability of these cells will facilitate the use of rat experimental models for functional studies of lymphatic endothelium.