Rabbit Anti-Human PDPN monoclonal antibody, clone KN42-32

Osteoarthritis (OA) is the most common degenerative joint disease characterized by articular cartilage degradation and joint degeneration. The articular cartilage is mainly formed by chondrocytes and a collagen-proteoglycan extracellular matrix that contains high levels of glycosylated proteins. It was reported that the shift from glycoproteins containing alpha-2,6-linked sialic acids to those that contain alpha-2,3 was associated with the onset of common types of arthritis. However, the pathophysiology of alpha-2,3-sialylation in cartilage has not been yet elucidated. We show that cartilage from osteoarthritic patients expresses high levels of the alpha-2,3-sialylated transmembrane mucin receptor, known as podoplanin (PDPN). Additionally, the Maackia amurensis seed lectin (MASL), that can be utilized to target PDPN, attenuates the inflammatory response mediated by NF-kB activation in primary chondrocytes and protects human cartilage breakdown ex vivo and in an animal model of arthritis. These findings reveal that specific lectins targeting alpha-2,3-sialylated receptors on chondrocytes might effectively inhibit cartilage breakdown. We also present a computational 3D molecular model for this interaction. These findings provide mechanistic information on how a specific lectin could be used as a novel therapy to treat degenerative joint diseases such as osteoarthritis.

Objectives: We assessed whether D2-40/podoplanin (PDPN) could be used to identify bladder cancer patients with a higher probability of benefiting from cisplatin-based combination chemotherapy. Patients and methods: We investigated PDPN expression by immunohistochemical analysis of cystectomy specimens from 96 bladder cancer patients who had undergone radical cystectomy without neoadjuvant or adjuvant cisplatin-based combination chemotherapy until recurrence. We classified the cases into 2 groups according to the achievement of 2-year recurrence-free survival (RFS) and evaluated whether PDPN expression was associated with patient prognosis. We also classified the 96 cases into 3 groups according to the possible need for perioperative chemotherapy based on the response to chemotherapy after recurrence as "unnecessary" (achieving 2-year RFS), "responder" (recurring within 2 years and responding to chemotherapy after recurrence), and "non-responder" (not responding chemotherapy following recurrence) and compared PDPN expression between these groups. Results: Among 13 cases diagnosed with clinically = 1% (log-rank tests). Moreover, the positive predictive value and specificity of a <1% PDPN positive staining ratio were 89.5% and 86.7%, respectively, for "unnecessary" perioperative chemotherapy in the 69 cases. Conclusion: Our results confirmed that cisplatin-based perioperative chemotherapy is unnecessary in many cases requiring radical cystectomy. To our knowledge, this is the first report of PDPN expression in bladder cancer stroma cells that are morphologically fibroblasts. Although PDPN expression might be associated with poor prognosis after surgery, we did not find that it helped to predict chemotherapy response. Whether PDPN expression by fibroblasts in high-risk bladder cancer cases is a marker for prognosis after radical cystectomy and response to perioperative cisplatin-based chemotherapy to avoid unnecessary chemotherapy warrants further investigation. (C) 2020 Elsevier Inc. All rights reserved.