scholarly journals The Met tyrosine kinase receptor as a therapeutic target and a potential cancer stem cell factor responsible for therapy resistance

2016 ◽  
Vol 37 (2) ◽  
pp. 647-656 ◽  
Author(s):  
Katarzyna Miekus
Cell ◽  
1990 ◽  
Vol 63 (1) ◽  
pp. 213-224 ◽  
Author(s):  
Krisztina M. Zsebo ◽  
David A. Williams ◽  
Edwin N. Geissler ◽  
Virginia C. Broudy ◽  
Francis H. Martin ◽  
...  

2018 ◽  
Author(s):  
Brittni M. Foster ◽  
Danish Zaidi ◽  
Tyler R. Young ◽  
Mary E. Mobley ◽  
Bethany A. Kerr

ABSTRACTMetastasis is the primary cause of cancer patient morbidity and mortality but due to persisting gaps in our knowledge, it remains untreatable. Metastases often occur as patients' tumors progress or recur after initial therapy. Tumor recurrence at the primary site may be driven by a cancer stem-like cell or tumor progenitor cell, while recurrence at a secondary site is driven by metastatic cancer stem cells or metastasis-initiating cells. Ongoing efforts are aimed at identifying and characterizing these stem-like cells driving recurrence and metastasis. One potential marker for the cancer stem-like cell subpopulation is CD117/c-kit, a tyrosine kinase receptor associated with cancer progression and normal stem cell maintenance. In our analyses, CD117 was expressed in several tissues and was highly expressed in bone marrow progenitor cells. Also, we uncovered that CD117 gene amplifications and mutations occurred in multiple cancers. Further, activation of CD117 by its ligand stem cell factor (SCF; kit ligand) in the progenitor cell niche stimulates several signaling pathways driving proliferation, survival, and migration. These signaling pathways were commonly altered in patients with CD117 amplifications and mutations. Here, we examine evidence that the SCF/CD117 signaling axis controls cancer progression through the regulation of stemness and resistance to tyrosine kinase inhibitors.AbbreviationsAMLacute myeloid leukemiaCMLchronic myeloid leukemiaCTCcirculating tumor cellCSCcancer stem cellDTCdisseminated tumor cellGISTgastrointestinal stromal tumorHSChematopoietic stem cellSCFstem cell factorTKItyrosine kinase inhibitor


2016 ◽  
Vol 16 (3) ◽  
pp. 301-307 ◽  
Author(s):  
Muhammad Vaseem Shaikh ◽  
Manika Kala ◽  
Manish Nivsarkar

2014 ◽  
Vol 33 (1) ◽  
pp. 425-432 ◽  
Author(s):  
SULAN LI ◽  
DONGLI YUE ◽  
XINFENG CHEN ◽  
LIPING WANG ◽  
JIEYAO LI ◽  
...  

1992 ◽  
Vol 175 (1) ◽  
pp. 245-255 ◽  
Author(s):  
B K Wershil ◽  
M Tsai ◽  
E N Geissler ◽  
K M Zsebo ◽  
S J Galli

Interactions between products of the mouse W locus, which encodes the c-kit tyrosine kinase receptor, and the Sl locus, which encodes a ligand for c-kit receptor, which we have designated stem cell factor (SCF), have a critical role in the development of mast cells. Mice homozygous for mutations at either locus exhibit several phenotypic abnormalities including a virtual absence of mast cells. Moreover, the c-kit ligand SCF can induce the proliferation and maturation of normal mast cells in vitro or in vivo, and also can result in repair of the mast cell deficiency of Sl/Sld mice in vivo. We now report that administration of SCF intradermally in vivo results in dermal mast cell activation and a mast cell-dependent acute inflammatory response. This effect is c-kit receptor dependent, in that it is not observed when SCF is administered to mice containing dermal mast cells expressing functionally inactive c-kit receptors, is observed with both glycosylated and nonglycosylated forms of SCF, and occurs at doses of SCF at least 10-fold lower on a molar basis than the minimally effective dose of the classical dermal mast cell-activating agent substance P. These findings represent the first demonstration in vivo that a c-kit ligand can result in the functional activation of any cellular lineage expressing the c-kit receptor, and suggest that interactions between the c-kit receptor and its ligand may influence mast cell biology through complex effects on proliferation, maturation, and function.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
J Liss ◽  
M Kuczynska ◽  
A Knight ◽  
K Lukaszuk

Abstract Study question To evaluate the correlation between the serum level of stem cell factor (s-SCF) during the stimulation and results of embryo culture. Summary answer The serum SCF concentration at the stimulation stage may be a potential predictor of IVF outcome in endometriosis patients. What is known already Stem cell factor (SCF) is a pleiotropic cytokine that affects the target cells via the c-kit receptor, a tyrosine kinase receptor. Recent evidence indicates that SCF and c-kit may play a role in regulation and growth of ovarian follicular function. It is unclear whether endometriosis primarily affects in vitro fertilization outcomes via oocyte quality. SCF is produced during the human follicular phase, immediately before the ovulatory phase, and may play an important role in folliculogenesis and in the mechanism of ovulation. It may reflect a successful stimulation with ample follicle maturation. Study design, size, duration This was a prospective case-control study and consisted four group of patients: 10 with endometriosis, 24 PCOs, 20 with normal (AMH 1.2–4.0 ng/ml) and 11 with lower (AMH<1.2 ng/ml) ovary reserve who were undergoing IVF treatment with the assessment of serum SCF concentration between August 2019 and March 2020 at INVICTA Fertility Centre, Poland. The age of the patients ranged from 22 to 42 years (median 34 years). Participants/materials, setting, methods s-SCF was measured in duplicate by enzyme-linked immunosorbent assay (ELISA) kit in 195 serum samples collected during ovarian stimulation on days 1 and 8 and on the day of oocyte retrieval. We analysed correlation between s-SCF level and formation of top quality (TQ) blastocysts on day 5 formation in the study groups. Main results and the role of chance We have compared mean level of s-SCF within each group dividing the patients into two subgroups – those with at least one TQ blastocyst (TQ) on day 5 vs. those with no TQ blastocysts (no-TQ). There were no significant differences in mean s-SCF level on day 1 of stimulation between no-TQ and TQ patients in PCOs, normal and lower ovary reserve groups (41.1 pg/ml vs. 40.9 pg/ml; 34.8 pg/ml vs. 38.9 pg/ml and 32.3pg/ml vs. 28.7 pg/ml respectively). The mean level of s-SCF in endometriosis patients was higher in case of no-TQ compared to the TQ subgroup and were 41.1 pg/ml and 29.1 pg/ml respectively. Also no significant differences were also observed in the mean level of s-SCF in the no-TQ and TQ subgroups on the 8 day of stimulation and pick-up in PCOs, normal and lower ovary reserve patients. However, again in the case of endometriosis patients, the mean level of s-SCF was significantly lower on the 8 day of stimulation (28.1 pg/ml vs. 49.1 pg/ml; p < 0.05) and pick-up day (33.4 pg/ml vs. 50.4 pg/ml; p < 0.005) in samples from patients who had at least one TQ blastocysts on day 5 of culture. Limitations, reasons for caution More data are required to confirm the corelation of s-SCF level and presence of top quality blastocysts in patients with endometriosis. Wider implications of the findings: Our study suggests that the level of serum SCF during ovarian stimulation in patients with endometriosis of less 30 pg/ml may potentially be a predictor for the chance of obtaining at least one top quality blastocyst on day 5 and thus a chance to successful treatment. Trial registration number Not applicable


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