Paracrine regulation of fibroblast aminopeptidase N/CD13 expression by keratinocyte-releasable stratifin

Lai, Amy; Ghaffari, Abdi; Li, Yunyuan; Ghahary, Aziz

doi:10.1002/jcp.22666

Cited by 11 publications

(15 citation statements)

References 45 publications

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“…Only a more careful quantitative evaluation of the mean fluorescence intensity revealed significant differences in the expression of three antigens, namely CD13, CD29, and CD49c, possibly reflecting the adaptation of C-MSCs to the specific colonic lamina propria microenvironment. In fact CD13 is an aminopeptidase mediating the interaction between epithelia and mesenchyma (Lai et al, 2011) while the CD29/CD49c integrin heterodimer is known to specifically bind extracellular matrix components (ECM) for adhesion, migration, and differentiation (Prowse et al, 2011). The differences observed are particularly relevant, considering that cell functions are not easily discernible at phenotype level, in line with recent views indicating noise (Chang et al, 2008;Enver et al, 2009) or oscillatory protein expression states (McBeath et al, 2004;Disher et al, 2009) even within homogeneous cell populations.…”

Section: Discussionmentioning

confidence: 70%

“…In fact CD13 is an aminopeptidase mediating the interaction between epithelia and mesenchyma (Lai et al, 2011) while the CD29/CD49c integrin heterodimer is known to specifically bind extracellular matrix components (ECM) for adhesion, migration, and differentiation (Prowse et al, 2011). In fact CD13 is an aminopeptidase mediating the interaction between epithelia and mesenchyma (Lai et al, 2011) while the CD29/CD49c integrin heterodimer is known to specifically bind extracellular matrix components (ECM) for adhesion, migration, and differentiation (Prowse et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

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Identity and ranking of colonic mesenchymal stromal cells

Signore

Cerio

Boe

et al. 2012

Journal Cellular Physiology

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Although ongoing clinical trials utilize systemic administration of bone-marrow mesenchymal stromal cells (BM-MSCs) in Crohn's disease (CD), nothing is known about the presence and the function of mesenchymal stromal cells (MSCs) in the normal human bowel. MSCs are bone marrow (BM) multipotent cells supporting hematopoiesis with the potential to differentiate into multiple skeletal phenotypes. A recently identified new marker, CD146, allowing to prospectively isolate MSCs from BM, renders also possible their identification in different tissues. In order to elucidate the presence and functional role of MSCs in human bowel we analyzed normal adult colon sections and isolated MSCs from them. In colon (C) sections, resident MSCs form a net enveloping crypts in lamina propria, coinciding with structural myofibroblasts or interstitial stromal cells. Nine sub-clonal CD146(+) MSC lines were derived and characterized from colon biopsies, in addition to MSC lines from five other human tissues. In spite of a phenotype qualitative identity between the BM- and C-MSC populations, they were discriminated and categorized. Similarities between C-MSC and BM-MSCs are represented by: Osteogenic differentiation, hematopoietic supporting activity, immune-modulation, and surface-antigen qualitative expression. The differences between these populations are: C-MSCs mean intensity expression is lower for CD13, CD29, and CD49c surface-antigens, proliferative rate faster, life-span shorter, chondrogenic differentiation rare, and adipogenic differentiation completely blocked. Briefly, BM-MSCs, deserve the rank of progenitors, whereas C-MSCs belong to the restricted precursor hierarchy. The presence and functional role of MSCs in human colon provide a rationale for BM-MSC replacement therapy in CD, where resident bowel MSCs might be exhausted or diverted from their physiological functions.

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Section: Discussionmentioning

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Identity and ranking of colonic mesenchymal stromal cells

Signore

Cerio

Boe

et al. 2012

Journal Cellular Physiology

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“…Originally identified as a surface marker on myeloid cells (13), CD13 is a widely expressed membrane-bound metalloprotease involved in pleiotropic functions, including enzymatic cleavage of peptides, antigen presentation, and signal transduction that ultimately mediate downstream biological phenomena such as cell adhesion, proliferation, and motility (14). Diverse cell subpopulations (e.g., fibroblasts, pericytes, epithelial cells, tumor-initiating cells, and stem cells) express CD13 (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis

Dondossola

Rangel

Guzman-Rojas

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13 + bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b + CD13 + myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b + CD13 + myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs. A ngiogenesis is a rate-limiting step in the development of many solid tumors, making it an attractive target for therapeutic intervention (1). Although pharmacologic modulation of angiogenesis has shown some clinical success, negative factors such as treatment-related plasticity, drug resistance, and tumor diversity have underscored the need for a better understanding of tumor-associated blood vessel formation at a mechanistic level (2). Tumor angiogenesis is a multifactorial process involving several different cell subtypes, especially tumor stromal endothelial cells, pericytes, carcinoma-associated fibroblasts (CAFs), and bone marrow-derived cells (BMDCs) (3, 4). A variety of immune cells directly support angiogenesis, including mast cells, tumor-associated macrophages (TAMs), and Tie2-expressing macrophages (TEMs) (5-7). Endothelial cells recruit inflammatory cells to the extravascular tissue by the expression of different leukocyte adhesion molecules. In turn, immune cells produce soluble factors, such as chemokines, cytokines, and proteases, that influence endothelial cell function and angiogenesis in a paracrine fashion (5). Other studies have shown that BMDCs have the ability to differentiate into endothelial cells, possibly by conversion first to endothelial progenitors (8-10).Proteases activate growth factors and inhibit suppressive factors within tumors and are central to the angiogenic process within the tumor microenvironment (11). Studies on the involvement of aminopeptidases in tumor progression and angiogenesis have revealed a role for aminopeptidase N (CD13) expressed by stromal cells (12). Originally identified as a surface marker on myeloid cells (13), CD13 is a widely expressed membrane-bound metalloprotease involved in pleiotropic functions, including enzymatic cleavage of peptides, antigen presentation, and signal transduction that ultimately mediate downstream biological phenomena such as cell adhesion, proliferation, and motility (14). Diverse cell subpopulations (e.g., fibroblasts, pericytes, epithelial cells, tumor-initiating cells, and st...

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“…As a result of the cooperation of mesenchyme and keratinocytes we demonstrated drastic changes in the expression of 14-3-3σ. 14-3-3σ is a specific epithelial protein, strongly expressed in differentiated keratinocytes [5,32]. Our studies demonstrated that the expression of this protein in keratinocytes depends on mesenchymal activity (mesenchyme-derived soluble factors).…”

Section: Effects Of 14-3-3σ On Hacat Cellsmentioning

confidence: 59%

Up-Regulation of 14-3-3σ in Hacat upon Co-Cultivation with HEPM

Magnucki¹,

Białek²,

Hammje³

et al. 2013

J Clin Exp Dermatol Res

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Background: To generate an in vitro system of the dermal epithelial-mesenchymal interaction we co-cultured HaCaT (keratinocytes) and HEPM (embryonic mesenchyme). This model allowed a local disjunction with preserved cell-cell communication. Methods: For the analysis of different protein expression patterns between co-and pure-cultured HaCaTs we performed 2D-electrophoresis and mass spectrometry. Afterwards the mass spectromertically identified protein 14-3-3σ was silenced by siRNA in HaCaT cells. Results: We analyzed 28 spots and found 17 different expressed mainly metabolic and cytoskeletal proteins. Interestingly, stratifin (14-3-3σ), maspin and Profilin-1 (PFN1) were up-regulated, whereas Peroxiredoxin-5 (PRDX5), PDZ-and-LIM-domain-protein-1 (CLIM1) and Annexin A1 (ANXA1) were decreased in co-cultured HaCaTs. The specific knock-down of 14-3-3σ resulted in a down-regulation of RhoA, Rac1/2/3, LIMK1 and phosphorylated cofilin, which are involved in cytoskeleton dynamics. Furthermore, reduction of 14-3-3σ coincided with significantly decreased proliferation rates and levels of Ki67. Conclusions: We concluded that the interaction with mesenchymal cells may initiate the alternation of epidermal precursor cells to differentiated keratinocytes, what was confirmed by the up-regulation of different keratins. Furthermore, 14-3-3σ may influence the proliferation-rate of keratinocytes via Rho GTPases.

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Paracrine regulation of fibroblast aminopeptidase N/CD13 expression by keratinocyte-releasable stratifin

Cited by 11 publications

References 45 publications

Identity and ranking of colonic mesenchymal stromal cells

Identity and ranking of colonic mesenchymal stromal cells

CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis

Up-Regulation of 14-3-3σ in Hacat upon Co-Cultivation with HEPM

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