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High αv Integrin Level of Cancer Cells Is Associated with Development of Brain Metastasis in Athymic Rats.

Abstract Brain metastases commonly occur in patients with malignant skin, lung and breast cancers resulting in high morbidity and poor prognosis. Integrins containing an αv subunit are cell adhesion proteins that contribute to cancer cell migration and cancer progression. We hypothesized that high expression of αv integrin cell adhesion protein promoted metastatic phenotypes in cancer cells.
PMID
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Authors

Mayor MeshTerms
Keywords

Integrin

brain metastasis

breast cancer

intetumumab

lung cancer

melanoma

Journal Title anticancer research
Publication Year Start




PMID- 28739685
OWN - NLM
STAT- MEDLINE
DA  - 20170725
DCOM- 20170810
LR  - 20170810
IS  - 1791-7530 (Electronic)
IS  - 0250-7005 (Linking)
VI  - 37
IP  - 8
DP  - 2017 Aug
TI  - High alphav Integrin Level of Cancer Cells Is Associated with Development of
      Brain Metastasis in Athymic Rats.
PG  - 4029-4040
AB  - BACKGROUND/AIM: Brain metastases commonly occur in patients with malignant skin, 
      lung and breast cancers resulting in high morbidity and poor prognosis. Integrins
      containing an alphav subunit are cell adhesion proteins that contribute to cancer
      cell migration and cancer progression. We hypothesized that high expression of
      alphav integrin cell adhesion protein promoted metastatic phenotypes in cancer
      cells. MATERIALS AND METHODS: Cancer cells from different origins were used and
      studied regarding their metastatic ability and intetumumab, anti-alphav integrin 
      mAb, sensitivity using in vitro cell migration assay and in vivo brain metastases
      animal models. RESULTS: The number of brain metastases and the rate of occurrence
      were positively correlated with cancer cell alphav integrin levels. High alphav
      integrin-expressing cancer cells showed significantly faster cell migration rate 
      in vitro than low alphav integrin-expressing cells. Intetumumab significantly
      inhibited cancer cell migration in vitro regardless of alphav integrin expression
      level. Overexpression of alphav integrin in cancer cells with low alphav integrin
      level accelerated cell migration in vitro and increased the occurrence of brain
      metastases in vivo. CONCLUSION: alphav integrin promotes brain metastases in
      cancer cells and may mediate early steps in the metastatic cascade, such as
      adhesion to brain vasculature. Targeting alphav integrin with intetumumab could
      provide clinical benefit in treating cancer patients who develop metastases.
CI  - Copyright(c) 2017, International Institute of Anticancer Research (Dr. George J. 
      Delinasios), All rights reserved.
FAU - Wu, Yingjen Jeffrey
AU  - Wu YJ
AD  - Department of Neurology, Oregon Health & Sciences University, Portland, OR,
      U.S.A.
FAU - Pagel, Michael A
AU  - Pagel MA
AD  - Veterans Administration Medical Center, Portland, OR, U.S.A.
FAU - Muldoon, Leslie L
AU  - Muldoon LL
AD  - Department of Neurology, Oregon Health & Sciences University, Portland, OR,
      U.S.A.
AD  - Department of Cell, Developmental & Cancer Biology, Oregon Health & Sciences
      University, Portland, OR, U.S.A.
FAU - Fu, Rongwei
AU  - Fu R
AD  - School of Public Health, Oregon Health & Sciences University, Portland, OR,
      U.S.A.
AD  - Department of Emergency Medicine, Oregon Health & Sciences University, Portland, 
      OR, U.S.A.
FAU - Neuwelt, Edward A
AU  - Neuwelt EA
AD  - Department of Neurology, Oregon Health & Sciences University, Portland, OR,
      U.S.A. [email protected]
AD  - Veterans Administration Medical Center, Portland, OR, U.S.A.
AD  - Department of Neurosurgery, Oregon Health & Sciences University, Portland, OR,
      U.S.A.
LA  - eng
PT  - Journal Article
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Integrin alphaV)
RN  - 0 (intetumumab)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Brain/metabolism/pathology
MH  - Brain Neoplasms/drug therapy/*genetics/pathology/secondary
MH  - Cell Adhesion/*genetics
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Integrin alphaV/biosynthesis/*genetics
MH  - Neoplasm Metastasis
MH  - Neoplasms/drug therapy/*genetics/pathology
MH  - Rats
OTO - NOTNLM
OT  - Integrin
OT  - brain metastasis
OT  - breast cancer
OT  - intetumumab
OT  - lung cancer
OT  - melanoma
EDAT- 2017/07/26 06:00
MHDA- 2017/08/11 06:00
CRDT- 2017/07/26 06:00
PHST- 2017/05/22 [received]
PHST- 2017/06/01 [revised]
PHST- 2017/06/14 [accepted]
AID - 37/8/4029 [pii]
PST - ppublish
SO  - Anticancer Res. 2017 Aug;37(8):4029-4040.