Abstract
NK cells are effector lymphocytes involved in tumor immunosurveillance; however, in patients with solidmalignancies,NKcells have compromised functions.Wehave previously reported that lung tumor-associated NKcells (TANKs; peripheralblood) andtumor-infiltratingNKcells (TINKs) showproangiogenic,decidualNK-like (dNK) phenotype. In this study, we functionally andmolecularly investigated TINKs and TANKs fromblood and tissue samples of patients with colorectal cancer (CRC), a neoplasmin which inflammation and angiogenesis have clinical relevance, and compared them to NK cells from controls and patients with nononcologic inflammatory bowel disease. CRC TINKs/TANKs showed decreased expression for the activatory marker NKG2D, impaired degranulation activity, a decidual-likeNKpolarization toward the CD56brightCD16dim/-2CD9+CD49+ subset. TINKs and TANKs secreted cytokines with proangiogenic activities, and induce endothelial cell proliferation, migration, adhesion, and the formation of capillary-like structures in vitro. dNK cells release specific proangiogenic factors; amongwhich, angiogenin and invasion-associated enzymes related to theMMP9-TIMP1/2 axis.Here,we describe, for the first time, to our knowledge, the expression of angiogenin,MMP2/9, and TIMP by TANKs in patients with CRC. This phenotype could be relevant to the invasive capabilities and proangiogenic functions of CRC-NK cells and become a novel biomarker. STAT3/STAT5 activation was observed in CRC-TANKs, and treatment with pimozide, a STAT5 inhibitor, reduced endothelial cell capability to form capillary-like networks, inhibiting VEGF and angiogenin production without affecting the levels of TIMP1, TIMP2, and MMP9, indicating that STAT5 is involved in cytokine modulation but not invasion-associated molecules. Combination of Stat5 orMMP inhibitors with immunotherapy could help repolarizeCRCTINKs and TANKs to anti-tumor antimetastatic ones.
| Original language | English |
|---|---|
| Pages (from-to) | 5365-5377 |
| Number of pages | 13 |
| Journal | FASEB Journal |
| Volume | 32 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2018 |
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Keywords
- Angiogenesis
- STAT signaling
- STAT3
- STAT5
- VEGF
ASJC Scopus subject areas
- Biotechnology
- Biochemistry
- Molecular Biology
- Genetics
Cite this
Angiogenin and the MMP9-TIMP2 axis are up-regulated in proangiogenic, decidual NK-like cells from patients with colorectal cancer. / Bruno, Antonino; Bassani, Barbara; D'Urso, Davide Giuseppe; Pitaku, Ilvana; Cassinotti, Elisa; Pelosi, Giuseppe; Boni, Luigi; Dominioni, Lorenzo; Noonan, Douglas M.; Mortara, Lorenzo; Albini, Adriana.
In: FASEB Journal, Vol. 32, No. 10, 01.10.2018, p. 5365-5377.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Angiogenin and the MMP9-TIMP2 axis are up-regulated in proangiogenic, decidual NK-like cells from patients with colorectal cancer
AU - Bruno, Antonino
AU - Bassani, Barbara
AU - D'Urso, Davide Giuseppe
AU - Pitaku, Ilvana
AU - Cassinotti, Elisa
AU - Pelosi, Giuseppe
AU - Boni, Luigi
AU - Dominioni, Lorenzo
AU - Noonan, Douglas M.
AU - Mortara, Lorenzo
AU - Albini, Adriana
PY - 2018/10/1
Y1 - 2018/10/1
N2 - NK cells are effector lymphocytes involved in tumor immunosurveillance; however, in patients with solidmalignancies,NKcells have compromised functions.Wehave previously reported that lung tumor-associated NKcells (TANKs; peripheralblood) andtumor-infiltratingNKcells (TINKs) showproangiogenic,decidualNK-like (dNK) phenotype. In this study, we functionally andmolecularly investigated TINKs and TANKs fromblood and tissue samples of patients with colorectal cancer (CRC), a neoplasmin which inflammation and angiogenesis have clinical relevance, and compared them to NK cells from controls and patients with nononcologic inflammatory bowel disease. CRC TINKs/TANKs showed decreased expression for the activatory marker NKG2D, impaired degranulation activity, a decidual-likeNKpolarization toward the CD56brightCD16dim/-2CD9+CD49+ subset. TINKs and TANKs secreted cytokines with proangiogenic activities, and induce endothelial cell proliferation, migration, adhesion, and the formation of capillary-like structures in vitro. dNK cells release specific proangiogenic factors; amongwhich, angiogenin and invasion-associated enzymes related to theMMP9-TIMP1/2 axis.Here,we describe, for the first time, to our knowledge, the expression of angiogenin,MMP2/9, and TIMP by TANKs in patients with CRC. This phenotype could be relevant to the invasive capabilities and proangiogenic functions of CRC-NK cells and become a novel biomarker. STAT3/STAT5 activation was observed in CRC-TANKs, and treatment with pimozide, a STAT5 inhibitor, reduced endothelial cell capability to form capillary-like networks, inhibiting VEGF and angiogenin production without affecting the levels of TIMP1, TIMP2, and MMP9, indicating that STAT5 is involved in cytokine modulation but not invasion-associated molecules. Combination of Stat5 orMMP inhibitors with immunotherapy could help repolarizeCRCTINKs and TANKs to anti-tumor antimetastatic ones.
AB - NK cells are effector lymphocytes involved in tumor immunosurveillance; however, in patients with solidmalignancies,NKcells have compromised functions.Wehave previously reported that lung tumor-associated NKcells (TANKs; peripheralblood) andtumor-infiltratingNKcells (TINKs) showproangiogenic,decidualNK-like (dNK) phenotype. In this study, we functionally andmolecularly investigated TINKs and TANKs fromblood and tissue samples of patients with colorectal cancer (CRC), a neoplasmin which inflammation and angiogenesis have clinical relevance, and compared them to NK cells from controls and patients with nononcologic inflammatory bowel disease. CRC TINKs/TANKs showed decreased expression for the activatory marker NKG2D, impaired degranulation activity, a decidual-likeNKpolarization toward the CD56brightCD16dim/-2CD9+CD49+ subset. TINKs and TANKs secreted cytokines with proangiogenic activities, and induce endothelial cell proliferation, migration, adhesion, and the formation of capillary-like structures in vitro. dNK cells release specific proangiogenic factors; amongwhich, angiogenin and invasion-associated enzymes related to theMMP9-TIMP1/2 axis.Here,we describe, for the first time, to our knowledge, the expression of angiogenin,MMP2/9, and TIMP by TANKs in patients with CRC. This phenotype could be relevant to the invasive capabilities and proangiogenic functions of CRC-NK cells and become a novel biomarker. STAT3/STAT5 activation was observed in CRC-TANKs, and treatment with pimozide, a STAT5 inhibitor, reduced endothelial cell capability to form capillary-like networks, inhibiting VEGF and angiogenin production without affecting the levels of TIMP1, TIMP2, and MMP9, indicating that STAT5 is involved in cytokine modulation but not invasion-associated molecules. Combination of Stat5 orMMP inhibitors with immunotherapy could help repolarizeCRCTINKs and TANKs to anti-tumor antimetastatic ones.
KW - Angiogenesis
KW - STAT signaling
KW - STAT3
KW - STAT5
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=85052154451&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85052154451&partnerID=8YFLogxK
U2 - 10.1096/fj.201701103R
DO - 10.1096/fj.201701103R
M3 - Article
AN - SCOPUS:85052154451
VL - 32
SP - 5365
EP - 5377
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 10
ER -