Abstract
Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases.
| Original language | English |
|---|---|
| Pages (from-to) | 10493-10501 |
| Number of pages | 9 |
| Journal | World Journal of Gastroenterology |
| Volume | 21 |
| Issue number | 37 |
| DOIs | |
| Publication status | Published - Oct 7 2015 |
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Keywords
- Angiogenesis
- Anti-angiogenic therapy
- Bone metastases
- C-kit receptor tyrosine kinase inhibitors
- Gastric cancer
- Osteoclastic bone resorption
- Receptor activator of nuclear factor-κB
- Tryptase inhibitors
ASJC Scopus subject areas
- Gastroenterology
Cite this
Targeting mast cells in gastric cancer with special reference to bone metastases 2015 advances in gastric cancer. / Leporini, Christian; Ammendola, Michele; Marech, Ilaria; Sammarco, Giuseppe; Sacco, Rosario; Gadaleta, Cosmo Damiano; Oakley, Caroline; Russo, Emilio; De Sarro, Giovambattista; Ranieri, Girolamo.
In: World Journal of Gastroenterology, Vol. 21, No. 37, 07.10.2015, p. 10493-10501.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting mast cells in gastric cancer with special reference to bone metastases 2015 advances in gastric cancer
AU - Leporini, Christian
AU - Ammendola, Michele
AU - Marech, Ilaria
AU - Sammarco, Giuseppe
AU - Sacco, Rosario
AU - Gadaleta, Cosmo Damiano
AU - Oakley, Caroline
AU - Russo, Emilio
AU - De Sarro, Giovambattista
AU - Ranieri, Girolamo
PY - 2015/10/7
Y1 - 2015/10/7
N2 - Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases.
AB - Bone metastases from gastric cancer (GC) are considered a relatively uncommon finding; however, they are related to poorer prognosis. Both primary GC and its metastatic progression rely on angiogenesis. Several lines of evidence from GC patients strongly support the involvement of mast cells (MCs) positive to tryptase (MCPT) in primary gastric tumor angiogenesis. Recently, we analyzed infiltrating MCs and neovascularization in bone tissue metastases from primary GC patients, and observed a significant correlation between infiltrating MCPT and angiogenesis. Such a finding suggested the involvement of peritumoral MCPT by infiltrating surrounding tumor cells, and in bone metastasis angiogenesis from primary GC. Thus, an MCPT-stimulated angiogenic process could support the development of metastases in bone tissue. From this perspective, we aim to review the hypothetical involvement of tumorinfiltrating, peritumoral MCPT in angiogenesis-mediated GC cell growth in the bone microenvironment and in tumor-induced osteoclastic bone resorption. We also focus on the potential use of MCPT targeting agents, such as MCs tryptase inhibitors (gabexate mesylate, nafamostat mesylate) or c-KitR tyrosine kinase inhibitors (imatinib, masitinib), as possible new anti-angiogenic and anti-resorptive strategies for the treatment of GC patients affected by bone metastases.
KW - Angiogenesis
KW - Anti-angiogenic therapy
KW - Bone metastases
KW - C-kit receptor tyrosine kinase inhibitors
KW - Gastric cancer
KW - Osteoclastic bone resorption
KW - Receptor activator of nuclear factor-κB
KW - Tryptase inhibitors
UR - http://www.scopus.com/inward/record.url?scp=84942783603&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942783603&partnerID=8YFLogxK
U2 - 10.3748/wjg.v21.i37.10493
DO - 10.3748/wjg.v21.i37.10493
M3 - Article
VL - 21
SP - 10493
EP - 10501
JO - World Journal of Gastroenterology
JF - World Journal of Gastroenterology
SN - 1007-9327
IS - 37
ER -