|
|
Autocrine proliferation of
neuroblastoma cells is partly mediated through neurokinin receptors:
relevance to bone marrow metastasis
Indroneil Mukerji, Shakti H. Ramkissoon,
Kavitha K. R. Reddy and Pranela Rameshwar
New Jersey
Medical School (UMDNJ-NJMS), Department of Medicine –
Hematology/Oncology, University of Medicine and Dentistry of New
Jersey, 185 South Orange Avenue, MSB, Room E-579, Newark, NJ 07103,
USA
Correspondence to: Pranela Rameshwar,
Email: rameshwa@umdnj.edu, Phone: +1-973-972-0625, Fax:
+1-973-972-8854.
Despite intensive therapy, ~60–80% of
children who are diagnosed with metastatic neuroblastoma (NB) succumb
to the disease.
NB preferentially metastasizes to the bone marrow (BM).
In the present study we used SY5Y and CHP212 (NB cell lines) to study
the roles of the preprotachykinin-I (PPT-I) gene and the natural
receptors for PPT-I peptides, neurokinin-1 (NK-1) and NK-2, in the
biology of NB.
PPT-I, NK-1 and NK-2 were constitutively expressed in the NB
cells.
Functional studies, with specific NK receptor antagonists, showed that
PPT-I peptides mediate autocrine proliferation of the NB cells through
both NK-1 and NK-2 receptors.
Full-length and truncated NK-1 receptors were detected in NB
cells.
Since there is one copy of the NK-1 gene, we used NK-1-specific siRNA
to suppress the expression of NK-1.
The NK-1-deficient NB cells showed phenotypes consistent with cell
differentiation.
Suppression of NK-1 did not appear to cause cell death, as
demonstrated by trypan blue exclusion and by undetectable active
caspase. NK-1 suppression reduced the proliferation of the NB cells
beginning by 10-fold at day 1 and reached a 105-fold
reduction by day 10.
The NK-1 deficient cells did not proliferate when they were placed as
cocultures with BM stroma, which suggests that NK-1 signaling is
important for the survival of NB cells in the BM.
The results show potential roles for NK receptors in the proliferation
of NB.
Keywords bone
marrow - neuroblastoma - neurokinin receptors - preprotachykinin-I
© Springer 2005
Source:
http://springerlink.metapress.com/openurl.asp?genre=article&eissn=1573-7373&volume=71&issue=2&spage=91
DOI: http://dx.doi.org/10.1007/s11060-004-9182-2
|
