3936

LCP1

lymphocyte cytosolic protein 1 (L-plastin);LCP1;lymphocyte cytosolic protein 1 (L-plastin)

L-plastin (Lymphocyte cytosolic protein 1) (LCP-1) (LC64P)|LCP-1|Lymphocyte cytosolic protein-1 (plasmin)|bA139H14.1 (lymphocyte cytosolic protein 1 (L-plastin))|epididymis secretory protein Li 37|plastin 2|plastin-2

13q14.3

protein-coding

L-plastin, a gene that codes for an actin-bundling protein, is upregulated in the metastatic colon cancer cell line SW620, when compared to its premetastatic counterpart SW480. The aim of our study was to characterise the effect of L-plastin overexpression on SW480 cells in the context of the acquisition of a metastatic phenotype. SW480 cell lines overexpressing L-plastin were established (SW480-LPL). Analysis of these cell lines revealed significantly higher rates of proliferation and invasion than the control cell line (SW480-Ctrl). In addition, the expression of E-cadherin was lost from SW480-LPL cells. Treatment of SW480-LPL cells with cytochalasin B, an inhibitor of endocytosis, attenuated the loss of E-cadherin expression in these cells. The association of L-plastin overexpression with an increased rate of proliferation and invasion, and loss of E-cadherin expression in the SW480 colon cancer cell line indicates that L-plastin plays an important mechanistic role in colorectal cancer metastasis (supplementary material for this article can be found on the International Journal of cancer website at http://www.interscience.wiley.com/jpages/0020-7136/suppmat/index.html).

OBJECTIVE: To investigate the clinical significance of plasmic L-plastin level in patients with colorectal cancer. METHODS: From March 2008 to March 2009, plasma samples were collected from 40 patients and 40 healthy controls. Plasmic L-plastin level was measured by ELISA kit and was compared to TIMP-1. RESULTS: Plasmic L-plastin level in patients with colorectal cancer was higher than that in healthy adults (1.662+/-0.386 vs. 0.485+/-0.085 mug/L, P<0.01). The sensitivity of L-plastin in the diagnosis of colorectal cancer was 67.5%, and the specificity was 80.6%. The Youden index was 0.481 and AUC was 0.772 (P<0.01). Plasmic L-plastin levels were associated with the tumor size (P=0.006), serosal penetration (F=4.687, P<0.05) and lymphatic metastasis (P<0.01). Compared to plasmic TIMP-1 level, L-plastin showed the same capability in indicating the depth of tumor. The specificity of L-plastin was better in indicating lymphatic metastasis (86% vs. 58%, chi2=4.2, P<0.05). CONCLUSIONS: Plasmic L-plastin level may serve as a potential marker in colorectal cancer.

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.

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.