Multiple intratumoral sources of kit ligand promote gastrointestinal stromal tumor.
Humans
Mice
Animals
Imatinib Mesylate
/ pharmacology
Gastrointestinal Stromal Tumors
/ drug therapy
Stem Cell Factor
/ genetics
Pyrimidines
/ pharmacology
Piperazines
/ pharmacology
Benzamides
/ pharmacology
Drug Resistance, Neoplasm
/ genetics
Proto-Oncogene Proteins c-kit
Mutation
Antineoplastic Agents
/ pharmacology
Journal
Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
16
01
2023
accepted:
05
07
2023
revised:
22
06
2023
medline:
21
8
2023
pubmed:
20
7
2023
entrez:
19
7
2023
Statut:
ppublish
Résumé
Gastrointestinal stromal tumor (GIST) is the most common human sarcoma and is typically driven by a single mutation in the Kit or PDGFRA receptor. While highly effective, tyrosine kinase inhibitors (TKIs) are not curative. The natural ligand for the Kit receptor is Kit ligand (KitL), which exists in both soluble and membrane-bound forms. While KitL is known to stimulate human GIST cell lines in vitro, we used a genetically engineered mouse model of GIST containing a common human KIT mutation to investigate the intratumoral sources of KitL, importance of KitL during GIST oncogenesis, and contribution of soluble KitL to tumor growth in vivo. We discovered that in addition to tumor cells, endothelia and smooth muscle cells produced KitL in Kit
Identifiants
pubmed: 37468679
doi: 10.1038/s41388-023-02777-5
pii: 10.1038/s41388-023-02777-5
doi:
Substances chimiques
Imatinib Mesylate
8A1O1M485B
Stem Cell Factor
0
Pyrimidines
0
Piperazines
0
Benzamides
0
Proto-Oncogene Proteins c-kit
EC 2.7.10.1
Antineoplastic Agents
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2578-2588Subventions
Organisme : NCI NIH HHS
ID : R01 CA102613
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA251063
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
Références
Joensuu H, DeMatteo RP. The management of gastrointestinal stromal tumors: a model for targeted and multidisciplinary therapy of malignancy. Annu Rev Med. 2012;63:247–58.
pubmed: 22017446
doi: 10.1146/annurev-med-043010-091813
Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 2005;11:4182–90.
pubmed: 15930355
doi: 10.1158/1078-0432.CCR-04-2245
Agaram NP, Besmer P, Wong GC, Guo T, Socci ND, Maki RG, et al. Pathologic and molecular heterogeneity in imatinib-stable or imatinib-responsive gastrointestinal stromal tumors. Clin Cancer Res. 2007;13:170–81.
pubmed: 17200352
doi: 10.1158/1078-0432.CCR-06-1508
Lyman SD, Jacobsen SE. c-kit ligand and Flt3 ligand: stem/progenitor cell factors with overlapping yet distinct activities. Blood. 1998;91:1101–34.
pubmed: 9454740
doi: 10.1182/blood.V91.4.1101
Huang E, Nocka K, Beier DR, Chu TY, Buck J, Lahm HW, et al. The hematopoietic growth factor KL is encoded by the Sl locus and is the ligand of the c-kit receptor, the gene product of the W locus. Cell 1990;63:225–33.
pubmed: 1698557
doi: 10.1016/0092-8674(90)90303-V
Lennartsson J, Ronnstrand L. Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev. 2012;92:1619–49.
pubmed: 23073628
doi: 10.1152/physrev.00046.2011
Reber L, Da Silva CA, Frossard N. Stem cell factor and its receptor c-Kit as targets for inflammatory diseases. Eur J Pharm. 2006;533:327–40.
doi: 10.1016/j.ejphar.2005.12.067
Huang EJ, Nocka KH, Buck J, Besmer P. Differential expression and processing of two cell associated forms of the kit-ligand: KL-1 and KL-2. Mol Biol Cell. 1992;3:349–62.
pubmed: 1378327
pmcid: 275535
doi: 10.1091/mbc.3.3.349
Heissig B, Hattori K, Dias S, Friedrich M, Ferris B, Hackett NR, et al. Recruitment of stem and progenitor cells from the bone marrow niche requires MMP-9 mediated release of kit-ligand. Cell. 2002;109:625–37.
pubmed: 12062105
pmcid: 2826110
doi: 10.1016/S0092-8674(02)00754-7
Miyazawa K, Williams DA, Gotoh A, Nishimaki J, Broxmeyer HE, Toyama K. Membrane-bound Steel factor induces more persistent tyrosine kinase activation and longer life span of c-kit gene-encoded protein than its soluble form. Blood. 1995;85:641–9.
pubmed: 7530502
doi: 10.1182/blood.V85.3.641.bloodjournal853641
Yasuda A, Sawai H, Takahashi H, Ochi N, Matsuo Y, Funahashi H, et al. Stem cell factor/c-kit receptor signaling enhances the proliferation and invasion of colorectal cancer cells through the PI3K/Akt pathway. Dig Dis Sci. 2007;52:2292–300.
pubmed: 17410437
doi: 10.1007/s10620-007-9759-7
Zhang W, Stoica G, Tasca SI, Kelly KA, Meininger CJ. Modulation of tumor angiogenesis by stem cell factor. Cancer Res. 2000;60:6757–62.
pubmed: 11118063
Hida T, Ueda R, Sekido Y, Hibi K, Matsuda R, Ariyoshi Y, et al. Ectopic expression of c-kit in small-cell lung cancer. Int J Cancer Suppl. 1994;8:108–9.
pubmed: 7515024
doi: 10.1002/ijc.2910570723
Krystal GW, Hines SJ, Organ CP. Autocrine growth of small cell lung cancer mediated by coexpression of c-kit and stem cell factor. Cancer Res. 1996;56:370–6.
pubmed: 8542594
Hayashi Y, Asuzu DT, Gibbons SJ, Aarsvold KH, Bardsley MR, Lomberk GA, et al. Membrane-to-nucleus signaling links insulin-like growth factor-1- and stem cell factor-activated pathways. PLoS One. 2013;8:e76822.
pubmed: 24116170
pmcid: 3792098
doi: 10.1371/journal.pone.0076822
Bono P, Krause A, von Mehren M, Heinrich MC, Blanke CD, Dimitrijevic S, et al. Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Blood. 2004;103:2929–35.
pubmed: 15070666
doi: 10.1182/blood-2003-10-3443
Hirano K, Shishido-Hara Y, Kitazawa A, Kojima K, Sumiishi A, Umino M, et al. Expression of stem cell factor (SCF), a KIT ligand, in gastrointestinal stromal tumors (GISTs): a potential marker for tumor proliferation. Pathol Res Pract. 2008;204:799–807.
pubmed: 18602222
doi: 10.1016/j.prp.2008.05.002
Theou-Anton N, Tabone S, Brouty-Boye D, Saffroy R, Ronnstrand L, Lemoine A, et al. Co expression of SCF and KIT in gastrointestinal stromal tumours (GISTs) suggests an autocrine/paracrine mechanism. Br J Cancer. 2006;94:1180–5.
pubmed: 16570044
pmcid: 2361250
doi: 10.1038/sj.bjc.6603063
Sommer G, Agosti V, Ehlers I, Rossi F, Corbacioglu S, Farkas J, et al. Gastrointestinal stromal tumors in a mouse model by targeted mutation of the Kit receptor tyrosine kinase. Proc Natl Acad Sci USA. 2003;100:6706–11.
pubmed: 12754375
pmcid: 164511
doi: 10.1073/pnas.1037763100
Hou XW, Bai CG, Liu XH, Qiu C, Huang L, Xu JJ, et al. Expression of stem cell factor in gastrointestinal stromal tumors: Implications for proliferation and imatinib resistance. Oncol Lett. 2013;5:552–8.
pubmed: 23420128
doi: 10.3892/ol.2012.1019
Kim TS, Cavnar MJ, Cohen NA, Sorenson EC, Greer JB, Seifert AM, et al. Increased KIT inhibition enhances therapeutic efficacy in gastrointestinal stromal tumor. Clin Cancer Res. 2014;20:2350–62.
pubmed: 24583793
pmcid: 4008656
doi: 10.1158/1078-0432.CCR-13-3033
Ding L, Saunders TL, Enikolopov G, Morrison SJ. Endothelial and perivascular cells maintain haematopoietic stem cells. Nature. 2012;481:457–62.
pubmed: 22281595
pmcid: 3270376
doi: 10.1038/nature10783
Da Silva CA, Heilbock C, Kassel O, Frossard N. Transcription of stem cell factor (SCF) is potentiated by glucocorticoids and interleukin-1beta through concerted regulation of a GRE-like and an NF-kappaB response element. FASEB J. 2003;17:2334–6.
pubmed: 14563684
doi: 10.1096/fj.03-0136fje
Grimaldi P, Capolunghi F, Geremia R, Rossi P. Cyclic adenosine monophosphate (cAMP) stimulation of the kit ligand promoter in sertoli cells requires an Sp1-binding region, a canonical TATA box, and a cAMP-induced factor binding to an immediately downstream GC-rich element. Biol Reprod. 2003;69:1979–88.
pubmed: 12904318
doi: 10.1095/biolreprod.103.019471
Hue J, Kim A, Song H, Choi I, Park H, Kim T, et al. IL-18 enhances SCF production of melanoma cells by regulating ROI and p38 MAPK activity. Immunol Lett. 2005;96:211–7.
pubmed: 15585325
doi: 10.1016/j.imlet.2004.08.008
Hollenbeck ST, Sakakibara K, Faries PL, Workhu B, Liu B, Kent KC. Stem cell factor and c-kit are expressed by and may affect vascular SMCs through an autocrine pathway. J Surg Res. 2004;120:288–94.
pubmed: 15234225
doi: 10.1016/j.jss.2004.01.005
Tieniber AD, Hanna AN, Do K, Wang L, Rossi F, DeMatteo RP. Molecular and immunologic techniques in a genetically engineered mouse model of gastrointestinal stromal tumor. J Vis Exp. 2022.
Rossi F, Ehlers I, Agosti V, Socci ND, Viale A, Sommer G, et al. Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor. Proc Natl Acad Sci USA. 2006;103:12843–8.
pubmed: 16908864
pmcid: 1568935
doi: 10.1073/pnas.0511076103
Vitiello GA, Bowler TG, Liu M, Medina BD, Zhang JQ, Param NJ, et al. Differential immune profiles distinguish the mutational subtypes of gastrointestinal stromal tumor. J Clin Investig. 2019;129:1863–77.
pubmed: 30762585
pmcid: 6486334
doi: 10.1172/JCI124108
Han ZB, Ren H, Zhao H, Chi Y, Chen K, Zhou B, et al. Hypoxia-inducible factor (HIF)-1 alpha directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF). Carcinogenesis. 2008;29:1853–61.
pubmed: 18339685
doi: 10.1093/carcin/bgn066
Cohen NA, Zeng S, Seifert AM, Kim TS, Sorenson EC, Greer JB, et al. Pharmacological inhibition of KIT activates MET signaling in gastrointestinal stromal tumors. Cancer Res. 2015;75:2061–70.
pubmed: 25836719
pmcid: 4467991
doi: 10.1158/0008-5472.CAN-14-2564
Treff NR, Dement GA, Adair JE, Britt RL, Nie R, Shima JE, et al. Human KIT ligand promoter is positively regulated by HMGA1 in breast and ovarian cancer cells. Oncogene. 2004;23:8557–62.
pubmed: 15378028
doi: 10.1038/sj.onc.1207926
Balachandran VP, Cavnar MJ, Zeng S, Bamboat ZM, Ocuin LM, Obaid H, et al. Imatinib potentiates antitumor T cell responses in gastrointestinal stromal tumor through the inhibition of Ido. Nat Med. 2011;17:1094–100.
pubmed: 21873989
pmcid: 3278279
doi: 10.1038/nm.2438
Asik M, Karakus S, Haznedaroglu IC, Goker H, Ozatli D, Buyukasik Y, et al. Bone marrow and peripheral blood C-kit ligand concentrations in patients with thrombocytosis and thrombocytopenia. Hematology. 2003;8:369–73.
pubmed: 14668031
doi: 10.1080/10245330310001621279
Horvath VJ, Vittal H, Lorincz A, Chen H, Almeida-Porada G, Redelman D, et al. Reduced stem cell factor links smooth myopathy and loss of interstitial cells of cajal in murine diabetic gastroparesis. Gastroenterology. 2006;130:759–70.
pubmed: 16530517
doi: 10.1053/j.gastro.2005.12.027
Tajima Y, Moore MA, Soares V, Ono M, Kissel H, Besmer P. Consequences of exclusive expression in vivo of Kit-ligand lacking the major proteolytic cleavage site. Proc Natl Acad Sci USA. 1998;95:11903–8.
pubmed: 9751763
pmcid: 21738
doi: 10.1073/pnas.95.20.11903
Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5:341–54.
pubmed: 15864276
doi: 10.1038/nrc1609
Matsumoto K, Umitsu M, De Silva DM, Roy A, Bottaro DP. Hepatocyte growth factor/MET in cancer progression and biomarker discovery. Cancer Sci. 2017;108:296–307.
pubmed: 28064454
pmcid: 5378267
doi: 10.1111/cas.13156
Okamoto W, Okamoto I, Tanaka K, Hatashita E, Yamada Y, Kuwata K, et al. TAK-701, a humanized monoclonal antibody to hepatocyte growth factor, reverses gefitinib resistance induced by tumor-derived HGF in non-small cell lung cancer with an EGFR mutation. Mol Cancer Ther. 2010;9:2785–92.
pubmed: 20716641
pmcid: 3208321
doi: 10.1158/1535-7163.MCT-10-0481
Yee NS, Hsiau CW, Serve H, Vosseller K, Besmer P. Mechanism of down-regulation of c-kit receptor. Roles of receptor tyrosine kinase, phosphatidylinositol 3'-kinase, and protein kinase C. J Biol Chem. 1994;269:31991–8.
pubmed: 7527401
doi: 10.1016/S0021-9258(18)31793-9
Shimizu Y, Ashman LK, Du Z, Schwartz LB. Internalization of Kit together with stem cell factor on human fetal liver-derived mast cells: new protein and RNA synthesis are required for reappearance of Kit. J Immunol. 1996;156:3443–9.
pubmed: 8617971
doi: 10.4049/jimmunol.156.9.3443
Lemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J. Kit receptor dimerization is driven by bivalent binding of stem cell factor. J Biol Chem. 1997;272:6311–7.
pubmed: 9045650
doi: 10.1074/jbc.272.10.6311
Liu H, Chen X, Focia PJ, He X. Structural basis for stem cell factor-KIT signaling and activation of class III receptor tyrosine kinases. EMBO J. 2007;26:891–901.
pubmed: 17255936
pmcid: 1794399
doi: 10.1038/sj.emboj.7601545
Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130:323–34.
pubmed: 17662946
doi: 10.1016/j.cell.2007.05.055
Krimmer SG, Bertoletti N, Suzuki Y, Katic L, Mohanty J, Shu S, et al. Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention. Proc Natl Acad Sci USA. 2023;120:e2300054120.
pubmed: 36943885
doi: 10.1073/pnas.2300054120
Huang Z, Ruan HB, Xian L, Chen W, Jiang S, Song A, et al. The stem cell factor/Kit signalling pathway regulates mitochondrial function and energy expenditure. Nat Commun. 2014;5:4282.
pubmed: 24999927
doi: 10.1038/ncomms5282
Merchant JL, Du M, Todisco A. Sp1 phosphorylation by Erk 2 stimulates DNA binding. Biochem Biophys Res Commun. 1999;254:454–61.
pubmed: 9918860
doi: 10.1006/bbrc.1998.9964
Minet E, Ernest I, Michel G, Roland I, Remacle J, Raes M, et al. HIF1A gene transcription is dependent on a core promoter sequence encompassing activating and inhibiting sequences located upstream from the transcription initiation site and cis elements located within the 5'UTR. Biochem Biophys Res Commun. 1999;261:534–40.
pubmed: 10425220
doi: 10.1006/bbrc.1999.0995
Toyota M, Hinoda Y, Takaoka A, Makiguchi Y, Takahashi T, Itoh F, et al. Expression of c-kit and kit ligand in human colon carcinoma cells. Tumour Biol. 1993;14:295–302.
pubmed: 7694350
doi: 10.1159/000217842
Bai C, Liu X, Qiu C, Zheng J. FoxM1 is regulated by both HIF-1alpha and HIF-2alpha and contributes to gastrointestinal stromal tumor progression. Gastric Cancer. 2019;22:91–103.
pubmed: 29948390
doi: 10.1007/s10120-018-0846-6
Huynh K. Meteorin-like protein repairs the ischaemic heart via receptor KIT in endothelial cells. Nat Rev Cardiol. 2022;19:575.
pubmed: 35817873
Medina BD, Liu M, Vitiello GA, Seifert AM, Zeng S, Bowler T, et al. Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity. J Exp Med. 2019;216:1359–76.
pubmed: 31000683
pmcid: 6547861
doi: 10.1084/jem.20180660
Tieniber AD, Hanna AN, Medina BD, Vitiello GA, Etherington MS, Liu M, et al. Tyrosine kinase inhibition alters intratumoral CD8 + T-cell subtype composition and activity. Cancer Immunol Res. 2022;10:1210–23.
pubmed: 35917579
pmcid: 10309533
doi: 10.1158/2326-6066.CIR-21-1039
Medina BD, Liu M, Vitiello GA, Seifert AM, Zeng S, Bowler T, et al. Oncogenic kinase inhibition limits Batf3-dependent dendritic cell development and antitumor immunity. J Exp Med. 2019;216:1359–76.
pubmed: 31000683
pmcid: 6547861
doi: 10.1084/jem.20180660
Seifert AM, Zeng S, Zhang JQ, Kim TS, Cohen NA, Beckman MJ, et al. PD-1/PD-L1 blockade enhances T-cell activity and antitumor efficacy of imatinib in gastrointestinal stromal tumors. Clin Cancer Res. 2017;23:454–65.
pubmed: 27470968
doi: 10.1158/1078-0432.CCR-16-1163
Vitiello GA, Medina BD, Zeng S, Bowler TG, Zhang JQ, Loo JK, et al. Mitochondrial inhibition augments the efficacy of imatinib by resetting the metabolic phenotype of gastrointestinal stromal tumor. Clin Cancer Res. 2018;24:972–84.
pubmed: 29246941
doi: 10.1158/1078-0432.CCR-17-2697
Satija R, Farrell JA, Gennert D, Schier AF, Regev A. Spatial reconstruction of single-cell gene expression data. Nat Biotechnol. 2015;33:495–502.
pubmed: 25867923
pmcid: 4430369
doi: 10.1038/nbt.3192
Hafemeister C, Satija R. Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol. 2019;20:296.
pubmed: 31870423
pmcid: 6927181
doi: 10.1186/s13059-019-1874-1
Liu M, Etherington MS, Hanna A, Medina BD, Vitiello GA, Bowler TG, et al. Oncogenic KIT modulates Type I IFN-mediated antitumor immunity in GIST. Cancer Immunol Res. 2021;9:542–53.
pubmed: 33648985
pmcid: 8102332
doi: 10.1158/2326-6066.CIR-20-0692