The MMP, matrilysin (MMP -7), has been shown to be overexpressed in prostate cancer cells and to ... more The MMP, matrilysin (MMP -7), has been shown to be overexpressed in prostate cancer cells and to increase prostate cancer cell invasion. Prostate stromal fibro- blasts secrete factor(s), including fibroblast growth factor -1 (FGF -1) that induces promatrilysin expression in LNCaP cells. In the present study, we investigated the signal transduction pathway involved in the FGF -1- induced expression of
Formal studies of skin cancer began more than 200 yr ago. The first skin tumor model to appear in... more Formal studies of skin cancer began more than 200 yr ago. The first skin tumor model to appear in the literature was reported by London surgeon Percivall Pott in 1775 (1). His account of scrotal cancer in chimney sweeps is considered the historical beginning of ...
Matrix metalloproteinases (MMPs) are involved in tumor progression. Matrilysin (MMP-7) has been s... more Matrix metalloproteinases (MMPs) are involved in tumor progression. Matrilysin (MMP-7) has been shown to be upregulated in prostatic carcinomas and can increase the invasive capacity of DU-145 cells. Because of the heterogenous nature of prostatic tumors, we examined promatrilysin expression in cocultures containing two different prostatic carcinoma cell lines, DU-145 and LNCaP. Using enzyme linked immunosorbent assay (ELISA) analyses, promatrilysin expression was measured in DU-145/LNCaP cocultures and conditioned media cross-cultures. The effects of blocking IL-6 on promatrilysin expression were examined by pretreating conditioned media with IL-6 neutralizing antibody. A significant induction of promatrilysin expression was observed in DU-145/LNCaP cocultures compared to LNCaP cells alone. In addition, DU-145 conditioned medium induced the same fold induction of promatrilysin as was observed in the cocultures. LNCaP cell conditioned medium did not induce promatrilysin expression in DU-145 cells. Neutralization of IL-6 with neutralizing antibody abrogated DU-145 conditioned media induced promatrilysin expression to baseline levels. IL-6 secreted by DU-145 cells can induce promatrilysin expression in LNCaP cells. IL-6, in vivo, may act as a paracrine signaling factor that regulates matrix metalloproteinase expression. Therefore, IL-6 may play a role in invasive metastatic processes of a prostate carcinoma.
Previously, our laboratory showed that interleukin-1β (IL-1β) secreted by lipopolysaccharide-acti... more Previously, our laboratory showed that interleukin-1β (IL-1β) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1β-induced promatrilysin expression is ...
Significant number of prostate tumors are slow growing and could probably be left untreated. Howe... more Significant number of prostate tumors are slow growing and could probably be left untreated. However, many are aggressive and can spread rapidly causing patient suffering and/or death. Current technology does not allow physicians to differentiate between slow growing and aggressive tumors at diagnosis. Hence, many patients are exposed to invasive treatment and its associated morbidities such as incontinence and impotence. Markers that enable differentiation between slow and fast progressing cancer will allow physicians to prevent unnecessary treatments on men who may not need them, and focus on the men with aggressive disease. A longitudinal study was conducted (N = 140) using mixed effects regression models to determine the association of obesity and smoking toward prostate cancer progression. These models account for correlation because of repeated measures over time, thus, using maximum amount of information provided by the subject. Estimates thus obtained are more robust and reliable than those obtained using data from a single time point. Rate of change of prostate-specific antigen (PSA) over time (PSA velocity) was used as a measure of prostate cancer progression. Results indicate that PSA velocity of overweight and obese subjects (0.59 and 1.05 ng/mL/year) was not significantly different as compared with normal weight subjects (p values .91 and .31, respectively). For men in the highest tertile of pack-years of smoking, PSA velocity was significantly higher as compared with never smokers 1.57 ng/mL/year (p = .04). Further studies with larger sample sizes and study designs specific to above exposures are needed before recommendations can be made to reduce weight or reduce/quit smoking.
The MMP, matrilysin (MMP -7), has been shown to be overexpressed in prostate cancer cells and to ... more The MMP, matrilysin (MMP -7), has been shown to be overexpressed in prostate cancer cells and to increase prostate cancer cell invasion. Prostate stromal fibro- blasts secrete factor(s), including fibroblast growth factor -1 (FGF -1) that induces promatrilysin expression in LNCaP cells. In the present study, we investigated the signal transduction pathway involved in the FGF -1- induced expression of
Formal studies of skin cancer began more than 200 yr ago. The first skin tumor model to appear in... more Formal studies of skin cancer began more than 200 yr ago. The first skin tumor model to appear in the literature was reported by London surgeon Percivall Pott in 1775 (1). His account of scrotal cancer in chimney sweeps is considered the historical beginning of ...
Matrix metalloproteinases (MMPs) are involved in tumor progression. Matrilysin (MMP-7) has been s... more Matrix metalloproteinases (MMPs) are involved in tumor progression. Matrilysin (MMP-7) has been shown to be upregulated in prostatic carcinomas and can increase the invasive capacity of DU-145 cells. Because of the heterogenous nature of prostatic tumors, we examined promatrilysin expression in cocultures containing two different prostatic carcinoma cell lines, DU-145 and LNCaP. Using enzyme linked immunosorbent assay (ELISA) analyses, promatrilysin expression was measured in DU-145/LNCaP cocultures and conditioned media cross-cultures. The effects of blocking IL-6 on promatrilysin expression were examined by pretreating conditioned media with IL-6 neutralizing antibody. A significant induction of promatrilysin expression was observed in DU-145/LNCaP cocultures compared to LNCaP cells alone. In addition, DU-145 conditioned medium induced the same fold induction of promatrilysin as was observed in the cocultures. LNCaP cell conditioned medium did not induce promatrilysin expression in DU-145 cells. Neutralization of IL-6 with neutralizing antibody abrogated DU-145 conditioned media induced promatrilysin expression to baseline levels. IL-6 secreted by DU-145 cells can induce promatrilysin expression in LNCaP cells. IL-6, in vivo, may act as a paracrine signaling factor that regulates matrix metalloproteinase expression. Therefore, IL-6 may play a role in invasive metastatic processes of a prostate carcinoma.
Previously, our laboratory showed that interleukin-1β (IL-1β) secreted by lipopolysaccharide-acti... more Previously, our laboratory showed that interleukin-1β (IL-1β) secreted by lipopolysaccharide-activated monocytes induces promatrilysin expression in the prostate carcinoma cell line, LNCaP. We now demonstrate that IL-1β-induced promatrilysin expression is ...
Significant number of prostate tumors are slow growing and could probably be left untreated. Howe... more Significant number of prostate tumors are slow growing and could probably be left untreated. However, many are aggressive and can spread rapidly causing patient suffering and/or death. Current technology does not allow physicians to differentiate between slow growing and aggressive tumors at diagnosis. Hence, many patients are exposed to invasive treatment and its associated morbidities such as incontinence and impotence. Markers that enable differentiation between slow and fast progressing cancer will allow physicians to prevent unnecessary treatments on men who may not need them, and focus on the men with aggressive disease. A longitudinal study was conducted (N = 140) using mixed effects regression models to determine the association of obesity and smoking toward prostate cancer progression. These models account for correlation because of repeated measures over time, thus, using maximum amount of information provided by the subject. Estimates thus obtained are more robust and reliable than those obtained using data from a single time point. Rate of change of prostate-specific antigen (PSA) over time (PSA velocity) was used as a measure of prostate cancer progression. Results indicate that PSA velocity of overweight and obese subjects (0.59 and 1.05 ng/mL/year) was not significantly different as compared with normal weight subjects (p values .91 and .31, respectively). For men in the highest tertile of pack-years of smoking, PSA velocity was significantly higher as compared with never smokers 1.57 ng/mL/year (p = .04). Further studies with larger sample sizes and study designs specific to above exposures are needed before recommendations can be made to reduce weight or reduce/quit smoking.
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