Sabato 27 ottobre 2012 - Pacini Editore

PoStER
Expression of ror-1 in pancreatic tumors
V. Toto 1 , M. Diodoro 2 , M. Mariotti 1 , R. Lattanzio 3 , R. La Sorda 3 ,
L. Stramucci 1 , P. Nisticò 4 , M. Piantelli 3 , E. Pescarmona 2 , M. Iezzi 1
1 Dipartimento di Medicina e Scienze dell’Invecchiamento, Sezione di
Anatomia Patologica e Medicina Molecolare, Centro Scienze dell’invecchiamento,
Fondazione Università G. d’Annunzio, Chieti; 2 Anatomia e
Istologia Patologica e Citodiagnostica, Regina Elena Istituto Nazionale
Tumori IRCCS, Roma; 3 Dipartimento di Scienze Biomediche, Sezione di
Patologia Oncologica, Centro Scienze dell’invecchiamento, Fondazione
Università G. d’Annunzio, Chieti; 4 Dipartimento Oncologia Sperimentale,
Laboratorio “B” di Immunologia, Regina Elena Istituto Nazionale
Tumori IRCCS, Roma
Introduction. Receptor tyrosine kinases (RTK) are transmembrane
proteins with ligand-controlled intracellular kinase activity.
They regulate several cellular activities such as the differentiation,
proliferation, migration, angiogenesis, survival, and communication
between cells. Ror1, an orphan tyrosine kinase, belongs
to the evolutionarily conserved RTK family of Ror, which also
includes Ror2. Ror1 is expressed during embryogenesis but not
by normal adult tissues. In tumors, Ror1 was indicated to be
overexpressed in certain leukemias, breast and lung cancers 1-4 .
Recently, Ror1 has emerged as a promising target of therapy
in leukemias by using of monoclonal antibodies 5 . In pancreatic
cancers, targeted therapies have been sporadically applied. Thus,
we have examined the expression of Ror1 in pancreatic cancer
specimens and cell lines to evaluate its clinical potential as therapeutic
target.
Material and methods. We have arranged in two Tissue Micro
Arrays (TMA) duplicate samples from 50 archivial primary pancreatic
tumors obtained at the “Regina Elena” National Cancer
Fig. 1.
Fig. 2. Examples of expression of Ror1 in pancreatic tumors.
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Institute (Rome, Italy) and “SS Annunziata” Hospital (Chieti,
Italy). Ror1 protein expression was assessed by FACS on pancreatic
cancer cell lines (PANC-1, CFPAC, L36PI) and by immunohistochemistry
on TMA.
Results. All pancreatic cancer cell lines expressed high levels of
Ror1 on cell membrane (Fig. 1). Immunohistochemically, Ror1
was not expressed in non-neoplastic pancreatic specimens. In
pancreatic tumors a diffuse immunoreactivity for Ror1 was found
in the cytoplasm of neoplastic cells (Figure 2). Forty-nine out of
50 (98.0%) tumors showed specific cytoplasmic immunoreactivity
for Ror1. The percentages of Ror1 positive tumor cells ranged
from 80 to 100, with a mean ± SE of 94.0 ± 2.6.
Conclusion. Ror1 protein expression is almost always present in
pancreatic tumors but is never expressed in non-neoplastic pancreatic
tissues. Thus, Ror1 is a potential target (to be validated as
predictive) of therapeutic drugs.
references
1 Baskar S, et al. Unique cell surface expression of receptor tyrosine
kinase ROR1 in human B-cell chronic lymphocytic leukemia. Clin
Cancer Res 2008;14:396-404.
2 Daneshmanesh AH, et al. Ror1, a cell surface receptor tyrosine kinase
is expressed in chronic lymphocytic leukemia and may serve as a putative
target for therapy. Int J Cancer 2008;123:1190-5.
3 Zhang S, et al. ROR1 is expressed in human breast cancer and associated
with enhanced tumor-cell growth. PLoS One 2012;7:e31127.
4 Yamaguchi T, et al. NKX2-1/TITF1/TTF-1-Induced ROR1 is required
to sustain EGFR survival signaling in lung adenocarcinoma. Cancer
Cell 2012;21:348-61.
5 Yang J, et al. Therapeutic potential and challenges of targeting receptor
tyrosine kinase ROR1 with monoclonal antibodies in B-cell
malignancies. PLoS One 2011;6:e21018.