Metastasis of prostate cancer and melanoma cells in a preclinical in vivo mouse model is enhanced by L-plastin expression and phosphorylation.

Abstract

BACKGROUND:

Tumor cell migration and metastasis require dynamic rearrangements of the actin cytoskeleton. Interestingly, the F-actin cross-linking and stabilizing protein L-plastin, originally described as a leukocyte specific protein, is aberrantly expressed in several non-hematopoietic malignant tumors. Therefore, it has been discussed as a tumor marker. However, systematic in vivo analyses of the functional relevance of L-plastin for tumor cell metastasis were so far lacking.

METHODS:

We investigated the relevance of L-plastin expression and phosphorylation by ectopical expression of L-plastin in human melanoma cells (MV3) and knock-down of endogenous L-plastin in prostate cancer (PC3M). The growth and metastatic potential of tumor cells expressing no L-plastin, phosphorylatable or non-phosphorylatable L-plastin was analyzed in a preclinical mouse model after subcutaneous and intracardial injection of the tumor cells.

RESULTS:

Knock-down of endogenous L-plastin in human prostate carcinoma cells led to reduced tumor cell growth and metastasis. Vice versa, and in line with these findings, ectopic expression of L-plastin in L-plastin negative melanoma cells significantly increased the number of metastases. Strikingly, the metastasis promoting effect of L-plastin was not observed if a non-phosphorylatable L-plastin mutant was expressed.

CONCLUSIONS:

Our data provide the first in vivo evidence that expression of L-plastin promotes tumor metastasis and, importantly, that this effect depends on an additionally required phosphorylation of L-plastin. In conclusion, these findings imply that for determining the importance of tumor-associated proteins like L-plastin a characterization of posttranslational modifications is indispensable.

• Authors: Selina M Riplinger, Guido H Wabnitz, Henning Kirchgessner, Beate Jahraus, Felix Lasitschka, Bianca Schulte, Gabri van der Pluijm, Geertje van der Horst, Günter J Hämmerling, Inaam Nakchbandi, Yvonne Samstag
• Journal: Molecular cancer (Mol Cancer) Vol. 13 Pg. 10 (Jan 18 2014) ISSN: 1476-4598 [Electronic] England
• PMID: 24438191 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Membrane Glycoproteins
• Microfilament Proteins
• plastin

Topics

• Animals
• Biomarkers, Tumor (metabolism)
• Blotting, Western
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation
• Cytoskeleton (metabolism)
• Gene Knockdown Techniques
• Humans
• Immunohistochemistry
• Male
• Melanoma (metabolism, pathology)
• Membrane Glycoproteins (metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microfilament Proteins (metabolism)
• Neoplasm Invasiveness
• Phosphorylation
• Prostatic Neoplasms (metabolism, pathology)
• Transfection
• Xenograft Model Antitumor Assays