XMRV Induces Cell Migration, Cytokine Expression and Tumor Angiogenesis

[Jemal]

XMRV Induces Cell Migration, Cytokine Expression and Tumor Angiogenesis: Are 22Rv1 Cells a Suitable Prostate Cancer Model?

22Rv1 is a common prostate cancer cell line used in xenograft mouse experiments as well as in vitro cell culture assays to study aspects of prostate cancer tumorigenesis. Recently, this cell line was shown to harbor multiple copies of a gammaretrovirus, called XMRV, integrated in its genome. While the original prostate cancer xenograft CWR22 is free of any retrovirus, subsequently generated cell lines 22Rv1 and CWR-R1, carry this virus and additionally shed infectious gammaretroviral particles in their supernatant. Although XMRV most likely was generated by recombination events in cell culture this virus has been demonstrated to infect human cells in vitro and 22Rv1 as well as CWR-R1 cells are now considered biosafety 2 reagents. Here, we demonstrate that 22Rv1 cells with reduced retroviral transcription show reduced tumor angiogenesis and increased necrosis of the primary tumor derived from xenografted cells in scid mice when compared to the parental cell line. The presence of XMRV transcripts significantly increases secretion of osteopontin (OPN), CXCL14, IL13 and TIMP2 in 22Rv1 cells. Furthermore, these data are supported by in vitro cell invasion and differentiation assays. Collectively, our data suggest that the presence of XMRV transcripts at least partially contributes to 22Rv1 characteristics observed in vitro and in vivo with regard to migration, invasion and tumor angiogenesis. We propose that data received with 22Rv1 cells or equivalent cells carrying xenotropic gammaretroviruses should be carefully controlled including other prostate cancer cell lines tested for viral sequences.

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042321?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed: plosone/Urology (PLoS ONE Alerts: Urology)

 

[Ember]

This statement in the discussion may be worthy of note: “XMRV-induced cytokine release does not appear to be tumor epithelial cell specific...”

 

[currer]

Looks like the XMRV is ramping up the cancer.

 

[natasa778]

Looks like the XMRV is ramping up the cancer.

Yes. Impressive little ability considering xmrv is a recently created chance contaminant.

I wonder how this links:

IDENTIFICATION OF A NOVEL RETROVIRUS IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

http://www.freepatentsonline.com/y2012/0107338.html

Disclosed herein are novel retroviruses associated with BPH and viral nucleic acids and polypeptides encoded by such nucleic acids. Also disclosed are methods of detecting presence of BPH virus in a sample from a subject and agents that can produce an immune response to a BPH virus that can be used for treatment and/or protection from a BPH virus infection. The BPH viruses disclosed herein are related to previously identified gammaretroviruses such as murine leukemia virus and xenotropic murine leukemia virus-related virus (XMRV), but are distinct from these viruses based on nucleic acid and amino acid sequences. Therefore, the methods disclosed herein include methods of specifically detecting BPH virus (such as a BPH virus polynucleotide or polypeptide) in a sample from a subject, for example discriminating the presence of BPH virus in a sample as opposed to XMRV. In some examples, the disclosed methods include detecting the presence of a BPH virus and the absence of XMRV in a sample from a subject.

 

[natasa778]

oh btw (even though retroviruses couldn´t possibly be causing neuroimmune diseases ) osteopontin is significantly raised in autism, and its levels correlate to severity of symptoms ...

The presence of XMRV transcripts significantly increases secretion of osteopontin (OPN)

 

[currer]

(From the paper) -" mice naturally do not develop PC"

anciendaze pointed this out on another forum.
Looks as if the mice could be immune to whatever is causing the PC- (remember they have evolved to be without the xpr1 receptor.)

 

[currer]

"We provide evidence that the gammaretrovirus XMRV significantly contributes to tumorigenesis of 22Rv1 xenografts in mice. These observations are supported by in vitro results demonstrating differences in cytokine release in 22Rv1 cells infected with XMRV and 22Rv1 cells with reduced viral transcripts. Furthermore, we provide evidence that XMRV infection in prostate stromal fibroblasts significantly induces changes in cytokine release"
...."In summary, our results indicate that the transforming capacity of 22Rv1 cells is strongly dependent on the presence of XMRV. "

 

[currer]

"BPH virus: A retrovirus identified in prostate samples from subjects with BPH.The BPH virus is distinct (for example at the nucleic acid or amino acid level) from XMRV"

From the above O'Keefe patent..(Thanks Nastasia.) Did we miss this patent when it was published? I dont remember it.

 

[currer]

oh btw (even though retroviruses couldn´t possibly be causing neuroimmune diseases ) osteopontin is significantly raised in autism, and its levels correlate to severity of symptoms ...

From Wiki -
"Osteopontin (OPN) is expressed in a range of immune cells, including macrophages, neutrophils, dendritic cells, and Tand B cells, with varying kinetics. OPN is reported to act as an immune modulator in a variety of manners. Firstly, it has chemitactic properties, which promote cell recruitment to inflammatory sites. It also functions as an adhesion protein, involved in cellattachment and wound healing In addition, OPN mediates cell activation and cytokine production, as well as promoting cell survival by regulating apoptosis"