Prior studies have documented that a majority of patients with juvenile periodontitis have suppressed polymorphonuclear leukocyte (PMN) chemotaxis. However, in other forms of earlyonset periodontitis, PMN migration has been studied only to a limited extent or not at all, and monocyte (MN) chemotaxis has not been extensively studied in patients with any of the forms of periodontitis. Accordingly, PMN and MN chemotaxis was studied in 7 patients with prepubertal, 37 with juvenile, and 35 with rapidly progressive periodontitis. In addition, PMN chemotaxis was studied in 8 patients with adult periodontitis. In the prepubertal group, 5 patients had abnormal PMN chemotaxis, 5 had depressed MN chemotaxis, and one had reduced serum chemotactic activity. All patients in this group had at least one form of leukocyte chemotaxis abnormality. In the juvenile periodontitis group, 17 patients had abnormal PMN responses, 16 of these were depressed while 1 was enhanced. MN chemotaxis was depressed in 4 of these patients and elevated in 2. Five patients had reduced serum chemotactic activity and one manifested a serum chemotactic inhibitor. In total, 65% of juvenile patients had some form of abnormality. In the rapidly progressive group, 15 had abnormal PMN chemotaxis, 7 had aberrant MN chemotaxis, 4 had reduced serum chemotactic activity, and 8 had a serum inhibitor of chemotaxis. No abnormalities were found in the PMNs or sera of patients with adult periodontitis. Overall, 66% of the early‐onset patients manifested some form of cell or serum‐related leukocyte chemotactic abnormality. Thus, abnormalities of leukocyte chemotaxis were present in all patients with prepubertal periodontitis and in a majority of those with juvenile and rapidly progressive disease, while no abnormalities were found in 8 patients with adult periodontitis.

Fibronectin (FN) is a core matrix protein that assembles to form a dynamic cellular scaffold, frequently perturbed during oncogenic transformation. Tumor hypoxia, characterized by low oxygen concentrations in the microenvironment of most solid tumors has been shown to accelerate FN assembly in fibroblasts and cancer-associated fibroblasts, cell types that produce abundant amounts of FN protein. Nevertheless, FN matrix regulation in epithelial cancer cells during hypoxia remains less well defined. In this study we investigate the assembly of the FN matrix during hypoxia in renal cancer epithelial cells, the cells of origin of renal cell carcinoma (RCC). We show that hypoxia (1% O2) specifically increases matrix disassembly and increases migratory propensity in renal cancer cells. However, HIFα stabilization using hypoxia mimetics, does not recapitulate the effect of hypoxia on FN matrix reorganization or cell migration. Using a combination of knockdown and inhibitor-based approaches, our work characterizes the signaling events that mediate these two disparate changes on the matrix and explores its functional significance on chemotactic cell migration. Our study systematically reexamines the role of hypoxia mimetics as experimental substitutes for hypoxia and provides new findings on HIFα stabilization and the FN matrix in the context of renal cancer.