Abstract
Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.
| Original language | English |
|---|---|
| Pages (from-to) | 2200-2206 |
| Number of pages | 7 |
| Journal | Cancer Research |
| Volume | 61 |
| Issue number | 5 |
| Publication status | Published - Mar 1 2001 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential. / Bellone, G.; Carbone, A.; Sibona, N.; Bosco, O.; Tibaudi, D.; Smirne, C.; Martone, T.; Gramigni, C.; Camandona, M.; Emanuelli, G.; Rodeck, U.
In: Cancer Research, Vol. 61, No. 5, 01.03.2001, p. 2200-2206.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Aberrant activation of c-kit protects colon carcinoma cells against apoptosis and enhances their invasive potential
AU - Bellone, G.
AU - Carbone, A.
AU - Sibona, N.
AU - Bosco, O.
AU - Tibaudi, D.
AU - Smirne, C.
AU - Martone, T.
AU - Gramigni, C.
AU - Camandona, M.
AU - Emanuelli, G.
AU - Rodeck, U.
PY - 2001/3/1
Y1 - 2001/3/1
N2 - Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.
AB - Multiple genetic aberrations contribute to the development of biologically aggressive, clinically malignant colorectal carcinomas (CRCs). Some of these have been linked to inappropriate signaling through the tyrosine kinase moieties of growth factor receptors. We have described previously (G. Bellone et al., J. Cell. Physiol., 172: 1-11, 1997) that human CRCs overexpress both the receptor tyrosine kinase c-kit and its ligand, stem cell factor (SCF), relative to normal mucosa cells, thus establishing an autocrine c-kit-mediated loop. In addition, we noted that exogenous SCF contributes to anchorage-independent growth of HT-29 colon carcinoma cells in semisolid medium. Here, we investigated possible roles of the c-kit/SCF autocrine/paracrine system in survival and invasive capacity of DLD-1 colon carcinoma cells. We report that SCF was required for migration and invasion of DLD-1 cells through reconstituted basement membranes (Matrigel) and up-regulated gelatinase (matrix metalloproteinase-9) activity in DLD-1 cells. Furthermore, we describe that SCF supported survival of DLD-1 cells in growth factor-deprived conditions. These results suggest multiple roles of c-kit activation in support of the malignant phenotype of DLD-1 cells related to growth, survival, migration, and invasive potential.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035266256&partnerID=8YFLogxK
M3 - Article
C2 - 11280787
AN - SCOPUS:0035266256
VL - 61
SP - 2200
EP - 2206
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 5
ER -