Ectopeptidases in pathophysiology

Antczak, Christophe; Meester, Ingrid De; Bauvois, Brigitte

doi:10.1002/1521-1878(200103)23:3<251::aid-bies1035>3.0.co;2-o

Cited by 65 publications

(90 citation statements)

References 63 publications

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“…membrane caveolae in different cell types (30,31). Furthermore, CD13 (as well as other ectopeptidases) may associate with other proteins into specific membrane regions (e.g., with certain integrins), thereby enabling CD13 to affect signaling processes, such as cell adhesion or apoptosis (32). Similar mechanisms have been described for many non-receptor tyrosine kinases present in caveolae (33).…”

Section: Discussionmentioning

confidence: 77%

Reduced Growth, Increased Vascular Area, and Reduced Response to Cisplatin in CD13-Overexpressing Human Ovarian Cancer Xenografts

Hensbergen¹,

Broxterman²,

Rana³

et al. 2004

Clinical Cancer Research

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Purpose: Expression of aminopeptidase N/CD13 can be detected in several solid tumor types. Thus far, the role of CD13 in ovarian cancer has not been studied. We have investigated the expression pattern and biological function of CD13 in ovarian cancer.Experimental Design: First, we studied the expression of CD13 in ovarian cancer tissue of 15 patients representing three different histological types (5 patients each) by immunohistochemistry. We then stably transfected the IGROV-1 human ovarian cancer cell line with a CD13 expression vector and examined the biological effect of CD13 in vitro and in vivo.Results: The expression of CD13 in ovarian cancer was associated with the histological subtype: CD13 expression in tumor cells was observed in 80 -100% of the patients with a serous or mucinous carcinoma and in only 20% of the clear cell carcinoma patients. In all patients' tumor samples, CD13-positive blood vessels were present. CD13 overexpression in IGROV-1 cells did not affect in vitro cell growth and sensitivity to doxorubicin, cisplatin, or gemcitabine. CD13 overexpression reduced invasion in Matrigel, which appeared to be independent of the aminopeptidase activity of CD13. Furthermore, the growth rate of IGROV-1/CD13 xenografts was reduced. The area of the vessel lumens was enlarged in a small percentage of vessels in the CD13-overexpressing xenografts. In addition, the CD13-overexpressing tumors were less sensitive to cisplatin.Conclusions: CD13 is expressed in tumor as well as endothelial cells in human ovarian cancer. Our results suggest that CD13 overexpression affects ovarian cancer growth, vascular architecture, and response to chemotherapy. Further elucidation of the mechanism of the observed effects of CD13 is warranted to better understand its role in the pathophysiology of ovarian cancer.

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Section: Discussionmentioning

confidence: 77%

Reduced Growth, Increased Vascular Area, and Reduced Response to Cisplatin in CD13-Overexpressing Human Ovarian Cancer Xenografts

Hensbergen¹,

Broxterman²,

Rana³

et al. 2004

Clinical Cancer Research

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“…204 It should be noticed that activation of MAPK pathways downstream of ectopeptidases converge with signal transduction pathways of other growth factor…”

Section: Overlap Of Ectopeptidase-and Fgfr2-mediated Signalingmentioning

confidence: 99%

“…214 receptors like FGFR2. 204 The activation status of cells of the pilosebaceous unit might be either downregulated by increasing IL-1ra and TGFβ by ectopeptidase inhibitors or decreasing IL-1α by inhibition of PKCα, PI3K/Akt and/or MAPK. 47,171 New options of therapeutic intervention in the treatment of acne should consider selective inhibition of FGFR2b-and IGF1R tyrosine kinase activity, the PI3K-Akt pathway, and ectopeptidases in acne-prone skin.…”

Section: Attenuation Of Fgfr2b-signal Transduction By Anti-acne Agentsmentioning

confidence: 99%

Role of FGFR2-signaling in the pathogenesis of acne

Melnik

2009

Dermato-Endocrinology

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It is the purpose of this review to extend our understanding of the fibroblast growth factor (FGF) receptor-2b-signaling network in the pathogenesis of acne. A new concept of the role of FGFR2b-signaling in dermal-epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, comedogenesis, sebaceous gland proliferation and lipogenesis is presented. The FGFR2-gain-of-function mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases pointing the way to androgen-dependent dermalepithelial FGFR2-signaling in acne. Androgen-mediated upregulation of FGFR2b-signaling in acne-prone skin appears to be involved in the pathogenesis of acne vulgaris. In organotypic skin cultures, keratinocyte-derived interleukin-1α stimulated fibroblasts to secrete FGF7 which stimulated FGFR2b-mediated keratinocyte proliferation. Postnatal deletion of FGFR2b in mice resulted in severe sebaceous gland atrophy. The importance of FGFR2b in sebaceous gland physiology is further supported by the mode of action of anti-acne agents which have been proposed to attenuate FGFR2b-signaling. Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity. Insulin-like growth factor-1 (IGF-1), the mediator of growth hormone during puberty, intracts with androgen-dependent FGFR2b-signaling and links androgen-and FGF-mediated signal transduction important in sebaceous gland homeostasis. The search for a follicular defect in the dermalepithelial regulation of growth factor-signaling in acne-prone skin appears to be a most promising approach to clarify the pathogenesis of acne.

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“…Thus, glucanases from diverse sources exhibit allergenic properties. Regarding Tri r 4, some S9 peptidases are involved in a variety of nonenzymatic physiologic processes; for example, the membrane glycoprotein dipeptidyl peptidase IV (DPPIV/ CD26) facilitates cell adhesion by interacting with collagen and fibronectin of the extracellular matrix via a cysteine-rich domain (6,22). DPPIV also processes bioactive peptides implicated in vascular permeability (22).…”

Section: Trichophyton Allergens: a Role For Enzymatic Function?mentioning

confidence: 99%

Allergy and Dermatophytes

Woodfolk

2005

Clin Microbiol Rev

143

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Tinea pedis (athlete's foot) and onychomycosis (infection of the toenails) caused by the dermatophyte fungus Trichophyton are highly prevalent in adults. Several Trichophyton allergens have been identified based on elicitation of immunoglobulin E antibody-mediated immediate-hypersensitivity (IH) responses. Evidence of an etiologic role for Trichophyton in asthma in some subjects with IH and chronic dermatophytosis is provided by bronchial reactivity to Trichophyton. Improvement of asthma after systemic antifungal treatment corroborates this link. A unique feature of Trichophyton allergens is the ability of the same antigen to elicit delayed-type hypersensitivity (DTH) in individuals who lack IH reactivity. Delayed responses appear to confer protection, while IH responses do not, based on the association with acute versus chronic skin infection. The amino acid sequence identity of Trichophyton allergens with diverse enzyme families supports a dual role for these proteins in fungal pathogenesis and allergic disease. Characterizing the immunologic properties of Trichophyton allergens and defining immune mechanisms which drive dichotomous responses are pivotal to understanding the dermatophyte-allergy relationship. Recent studies have identified DTH-associated major T-cell epitopes which could facilitate the development of peptide vaccines. Characterization of additional molecular targets by using new techniques may aid not only in the eradication of infection but also in the resolution of allergic symptoms

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Ectopeptidases in pathophysiology

Cited by 65 publications

References 63 publications

Reduced Growth, Increased Vascular Area, and Reduced Response to Cisplatin in CD13-Overexpressing Human Ovarian Cancer Xenografts

Reduced Growth, Increased Vascular Area, and Reduced Response to Cisplatin in CD13-Overexpressing Human Ovarian Cancer Xenografts

Role of FGFR2-signaling in the pathogenesis of acne

Allergy and Dermatophytes

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