Cancer cell metastasis is induced by actin-dependent cell migration and is affected by cytoskeletal remodelling proteins. FMNL2 is one such protein which promotes colorectal cancer (CRC) cell metastasis and amoeboid style invasion of melanoma cells. FMNL2 mRNA is subject to alternative splicing and studies suggest that the resulting encoded proteins are likely to differ in their regulation, subcellular localization and activity. We identified four FMNL2 isoforms (ITM, YHY, PMR and TQS) expressed in non-invasive (SW480) and invasive (SW620) CRC cells, as well as in highly invasive A375 amoeboid melanoma cells. qPCR data suggests that an “invasive” isoform (TQS) may be preferentially expressed in highly invasive and amoeboid cell lines. Boyden chamber invasion assay results show that FMNL2 knockdown inhibits amoeboid style invasion in two melanoma cell lines and that TQS is the most efficient isoform at rescuing the invasive phenotype. This study provides a further understanding of FMNL2’s role in invasion and metastasis and identifies specific targets for the development of future antimetastatic therapies.

Cancer cell metastasis is induced by actin-dependent cell migration and is affected by cytoskeletal remodelling proteins. FMNL2 is one such protein which promotes colorectal cancer (CRC) cell metastasis and amoeboid style invasion of melanoma cells. FMNL2 mRNA is subject to alternative splicing and studies suggest that the resulting encoded proteins are likely to differ in their regulation, subcellular localization and activity. We identified four FMNL2 isoforms (ITM, YHY, PMR and TQS) expressed in non-invasive (SW480) and invasive (SW620) CRC cells, as well as in highly invasive A375 amoeboid melanoma cells. qPCR data suggests that an “invasive” isoform (TQS) may be preferentially expressed in highly invasive and amoeboid cell lines. Boyden chamber invasion assay results show that FMNL2 knockdown inhibits amoeboid style invasion in two melanoma cell lines and that TQS is the most efficient isoform at rescuing the invasive phenotype. This study provides a further understanding of FMNL2’s role in invasion and metastasis and identifies specific targets for the development of future antimetastatic therapies.

<p>Background. Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas in the pleura. Cytokeratin 20 and 7 have been used successfully as markers in studies determining primary location of adenocarcinomas from metastases. The current study is a complementary research of archived paraffininbedded material of cases with cancer origin. This study contributes a bigger statistical material that may facilitate the search for unknown primary site of adenocarcinoma by identification of metastatic cells in the pleura.</p><p>Methods. Cells from the pleura taken from fifteen patients with diagnosed cancer of different types and eleven patients with cancer of unknown origin, were stained with antibodies against the tumour markers: Ber EP 4, calretinin, cytokeratin 20 and 7, estrogen receptor α, thyroid transcription factor, prostate-specific antigen and Cdx2.The staining was conducted in an automated immunohistochemical system. The staining of each kind of antibody was confirmed by a control section staining.</p><p>Results. All control staining ended perfect The whole panel of antibodies used on mammary cancer showed the same pattern for every antibody. Of the patients with cancer of unknown origin there were four that gave the same pattern, two men and two women. The women are deceased. To make a more careful evaluation more information and clinic background is needed. The number of samples is too small to draw any statistical conclusions.</p><p>Comment. Although the control staining was perfect the negative result of CK20 in the cases of diagnosed colon cancer was unexpected. This staining should be performed again to confirm the result. In some cases the number of cells were to few for a certain evaluation. The slides and the results of this work will be archived for further research.</p>

Yes / Tumor progression alters the composition and physical properties of the extracellular matrix. Particularly, increased matrix stiffness has profound effects on tumor growth and metastasis. While endothelial cells are key players in cancer progression, the influence of tumor stiffness on the endothelium and the impact on metastasis is unknown. Through quantitative mass spectrometry, we find that the matricellular protein CCN1/CYR61 is highly regulated by stiffness in endothelial cells. We show that stiffness-induced CCN1 activates β-catenin nuclear translocation and signaling and that this contributes to upregulate N-cadherin levels on the surface of the endothelium, in vitro This facilitates N-cadherin-dependent cancer cell-endothelium interaction. Using intravital imaging, we show that knockout of Ccn1 in endothelial cells inhibits melanoma cancer cell binding to the blood vessels, a critical step in cancer cell transit through the vasculature to metastasize. Targeting stiffness-induced changes in the vasculature, such as CCN1, is therefore a potential yet unappreciated mechanism to impair metastasis. / Cancer Research UK (CRUK Beatson Institute C596/A17196, CRUK Glasgow Centre C596/A18076 and S.Z. C596/A12935)

Background. Immunohistochemistry is a useful method in the differential diagnosis between pleural mesotheliomas and metastatic adenocarcinomas in the pleura. Cytokeratin 20 and 7 have been used successfully as markers in studies determining primary location of adenocarcinomas from metastases. The current study is a complementary research of archived paraffininbedded material of cases with cancer origin. This study contributes a bigger statistical material that may facilitate the search for unknown primary site of adenocarcinoma by identification of metastatic cells in the pleura. Methods. Cells from the pleura taken from fifteen patients with diagnosed cancer of different types and eleven patients with cancer of unknown origin, were stained with antibodies against the tumour markers: Ber EP 4, calretinin, cytokeratin 20 and 7, estrogen receptor α, thyroid transcription factor, prostate-specific antigen and Cdx2.The staining was conducted in an automated immunohistochemical system. The staining of each kind of antibody was confirmed by a control section staining. Results. All control staining ended perfect The whole panel of antibodies used on mammary cancer showed the same pattern for every antibody. Of the patients with cancer of unknown origin there were four that gave the same pattern, two men and two women. The women are deceased. To make a more careful evaluation more information and clinic background is needed. The number of samples is too small to draw any statistical conclusions. Comment. Although the control staining was perfect the negative result of CK20 in the cases of diagnosed colon cancer was unexpected. This staining should be performed again to confirm the result. In some cases the number of cells were to few for a certain evaluation. The slides and the results of this work will be archived for further research.