The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Dog mastocytoma cells secrete a 92-kD gelatinase activated extracellularly by mast cell chymase.
Open accessAbstract
Gelatinolytic metalloproteinases implicated in connective tissue remodeling and tumor invasion are secreted from several types of cells in the form of inactive zymogens. In this report, characterization of gelatinase activity secreted by the BR line of dog mastocytoma cells reveals a phorbol-inducible, approximately 92-kD, Ca2+ - and Zn2+ -dependent proenzyme cleaved over time to smaller, active forms. Incubation of cells with the general serine protease inhibitor, PMSF, prevented proenzyme cleavage and permitted its purification free of activation products. The NH2-terminal 13 amino acids of the purified mastocytoma progelatinase are 50-67% identical to those of human, mouse, and rabbit 92-kD progelatinase (gelatinase B; matrix metalloproteinase-9). Degranulation of mastocytoma cells using ionophore A23187 greatly accelerated proenzyme cleavage, suggesting that a serine protease present in secretory granules hydrolyzed the progelatinase to active fragments. To identify the activating protease, cells were coincubated with ionophore and a panel of selective serine protease inhibitors. Soybean trypsin inhibitor and succinyl-L-Ala-Ala-Pro-Phe-chloromethylketone, which inhibit mast cell chymase, prevented progelatinase activation. Inhibitors of tryptase and dog mast cell protease (dMCP)-3, i.e., aprotinin or bis(5-amidino-2-benzimidazolyl) methane (BABIM), did not. In further experiments using highly purified enzymes, mastocytoma cell chymase activated 92-kD progelatinase in the absence of other enzymes or cofactors; tryptase and dMCP-3, however, had no effect. These data demonstrate that dog mastocytoma cells secrete a metalloproteinase related to progelatinase B that is directly activated outside of the cell by exocytosed chymase, and provide the first demonstration of a cell that activates a matrix metalloproteinase it secretes by cosecreting an activating enzyme. In mastocytomas, this pathway may facilitate tumor invasion of surrounding tissues, and in normal mast cells, it could play a role in tissue remodeling and repair.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Moreover, MC tryptases and chymases have been shown to activate the precursors of MMP2 [12], MMP9 [13], collagenase and stromelysin [14].”
From Estradiol and Progesterone Regulate the Migration of Mast Cells from the Periphery to the Uterus and Induce Their Maturation and Degranulation (2010) · cites this paper as [13]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
A matrix metalloproteinase expressed on the surface of invasive tumour cells
Sato, H., Takino, T., Okada, Y., Cao, J. P., Shinagawa, A., Yamamoto, E., & Seiki, M. (1994) · Nature · doi:10.1038/370061a0 · Cited by 2,534
Metalloproteinases and their inhibitors in matrix remodeling
Matrisian, L. M. (1990) · Trends in Genetics · doi:10.1016/0168-9525(90)90126-q · Cited by 1,626
Van Wart, H. E., & Birkedal-Hansen, H. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.14.5578 · Cited by 1,475
Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase
Kjeldsen, L., Johnsen, A., Sengeløv, H., & Borregaard, N. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82217-7 · Cited by 1,286
Wilhelm, S. M., Collier, I. E., Marmer, B. L., Eisen, A. Z., Grant, G. A., & Goldberg, G. I. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71480-4 · Cited by 1,109
Tissue Inhibitor of Metalloproteinase (TIMP-2)
Stetler‐Stevenson, W. G., Krutzsch, H. C., & Liotta, L. A. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)71503-2 · Cited by 900
Springman, E. B., Angleton, E. L., Birkedal‐Hansen, H., & Wart, H. E. V. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.1.364 · Cited by 713
Ogata, Y., Enghild, J. J., & Nagase, H. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50563-4 · Cited by 629
Furin-dependent intracellular activation of the human stromelysin-3 zymogen
Pei, D., & Weiss, S. J. (1995) · Nature · doi:10.1038/375244a0 · Cited by 629
Biochemical and immunological characterization of the secreted forms of human neutrophil gelatinase.
Hibbs, M. S., Hasty, K. A., Seyer, J. M., Kang, A. H., & Mainardi, C. L. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89580-1 · Cited by 613
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–126 of 126
The Multiple Mechanistic Faces of a Pure Volume Overload: Implications for Therapy
Barnes, J. A., Dell’Italia, L. J., & Weber, K. T. (2014) · The American Journal of the Medical Sciences · doi:10.1097/maj.0000000000000255 · Cited by 8
Kinoshita, I., Jin, D., Higashino, M., Terada, T., Kurisu, Y., Takai, S., & Kawata, R. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312613 · Cited by 7
Iba, Y., Shirai, M., Dei, C., Hirata, T., Harada, C., & Masukawa, T. (2007) · International Immunopharmacology · doi:10.1016/j.intimp.2006.12.012 · Cited by 7
Mast cell chymase has a negative impact on human osteoblasts
Lind, T., Melo, F. R., Gustafson, A., Sundqvist, A., Zhao, X. O., Moustakas, A., Melhus, H., & Pejler, G. (2022) · Matrix Biology · doi:10.1016/j.matbio.2022.07.005 · Cited by 6
Inhibitors of human mast cell serine proteases and potential therapeutic applications
Rice, K., & Spencer, J. R. (1999) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.9.11.1537 · Cited by 6
Increased Chymase-Positive Mast Cells in High-Grade Mucoepidermoid Carcinoma of the Parotid Gland
Nishimura, H., Jin, D., Kinoshita, I., Taniuchi, M., Higashino, M., Terada, T., Takai, S., & Kawata, R. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098267 · Cited by 5
Khatami, M. (2017) · Springer eBooks · doi:10.1007/978-3-319-66475-0_2 · Cited by 5
Mast Cell and Eosinophil Proteases in the Chronic Allergic Inflammatory Response
Walls, A. F., Shute, J. K., Warner, J., Cairns, J. A., Howarth, P. H., & Holgate, S. T. (1998) · Elsevier eBooks · doi:10.1016/b978-012473340-4/50013-8 · Cited by 5
Protease Inhibitors for the Potential Treatment of Chronic Obstructive Pulmonary Disease and Asthma
Liu, W., & Hickey, E. R. (2008) · Annual reports in medicinal chemistry · doi:10.1016/s0065-7743(08)00011-0 · Cited by 4
dos Reis, C. A., Soares, M. A. D. M., & Gomes, J. R. (2019) · The Anatomical Record · doi:10.1002/ar.24314 · Cited by 4
Zuo, Y., Tracey, D. J., & Geczy, C. L. (2005) · NeuroImmunoModulation · doi:10.1159/000085653 · Cited by 4
Effect of chymase activity on skin thickness in the Clawn miniature pig hypertrophic scarring model
Jimi, S., & Matsumura, H. (2017) · Journal of Plastic Surgery and Hand Surgery · doi:10.1080/2000656x.2017.1310733 · Cited by 3
Taniguchi, S., Jin, D., Morihara, H., Yokoe, S., Moriwaki, K., & Takai, S. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178236 · Cited by 2
Detection of matrix metalloproteinase -2 and -9 in various types of canine tumours
Krupakaran, R. P., Balamurugan, T., SHEEBA, A., LAKSHMI, R. D., & PERUMAL, P. (2016) · The Indian Journal of Animal Sciences · doi:10.56093/ijans.v86i9.61540 · Cited by 2
Matrix Metalloproteinases: Mediators of Tumour-Host Cell Interactions
Diaz, R. J., Eichten, A., de Visser, K. E., & Coussens, L. M. (2005) · Springer eBooks · doi:10.1007/1-4020-3414-8_6 · Cited by 2
The Role of Mast Cells in Innate Immunity
Boyce, J. A., & Austen, K. F. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-320-0_20 · Cited by 1
Potential Mechanisms of Mast Cell Activation in Human Atherosclerotic Coronary Arteries
Laine, P. (2003) · Työväentutkimus Vuosikirja
(2013) · webmedcentralplus · doi:10.9754/journal.wplus.2013.0074
Lindstedt, L. (2000) · Työväentutkimus Vuosikirja
Poništ, S., Pružinská, K., & Bauerová, K. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.99073
Li, N., Xue, Y., Zhang, Q.-M., Xu, Y., Huihui, X., & Yang, Y. (2025) · The FASEB Journal · doi:10.1096/fj.202501651rrr
Biological functions and regulation of serglycin-dependent mast cell proteases
Lundequist, A. (2006) · Epsilon Open Archive (Sveriges lantbruksuniversitet biblioteket (Swedish University of Agricultural Sciences))
Reimer, J. M. (2008) · KTH Publication Database DiVA (KTH Royal Institute of Technology)
Renoprotective Effects of Chymase Inhibition on Cisplatin-Induced Nephrotoxicity in Mice
Yoshimoto, M., Jin, D., Sakonjo, H., & Takai, S. (2024) · Institutional Repositories DataBase (IRDB)
Insulin-Regulated Amino Peptidase (IRAP) controls FcR-mediated signaling and inflammatory responses
Bratti, M. (2021) · theses.fr (ABES) · doi:10.70675/cbdb8b72zd1adz47d8z8825ze4395bdc852f
Renoprotective Effects of Chymase Inhibition on Cisplatin-Induced Nephrotoxicity in Mice
吉本, 将. (n.d.) · Institutional Repositories DataBase (IRDB) · doi:10.57371/0002000442
Metadata
- Authors
- Fang, K. C., Raymond, W. W., Lazarus, S. C., & Caughey, G. H.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1996-04-01
- Volume
- 97
- Issue
- 7
- Pages
- 1589-1596
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC507221
- OpenAlex
- W1967763193
- Cited by
- 125
- References
- 40
- Citations by year
- 2025: 2 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 3 · 2019: 8 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 7 · 2013: 2 · 2012: 5
- FWCI
- 1.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Lung Association
- National Institutes of Health (HL24136)
- National Heart, Lung, and Blood Institute (F32HL009133, HL 24136, P01HL024136, HL 07185, HL09133)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Protease and Inhibitor Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Veterinary › Small Animals › Veterinary Oncology Research
- Keywords
- mastocytoma, chymase, MMP-9, serine protease, mast cell degranulation, tumor invasion, connective tissue remodeling, tryptase
- MeSH terms
- Amino Acid Sequence, Animals, Dogs, Enzyme Activation, Enzyme Inhibitors, Humans, Mast Cells, Molecular Sequence Data, Molecular Weight, Rabbits, Mast-Cell Sarcoma, Serine Endopeptidases, Tumor Cells, Cultured, Sequence Homology, Amino Acid, Gelatinases, Mice, Chymases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
