The tumour suppressive role of metastasis suppressor-1, MTSS1, in human kidney cancer, a possible connection with the SHH pathway.
BACKGROUND
Metastasis suppressor 1 (MTSS1), a cytoskeletal associated protein, has been indicated in certain types of human cancers, but its role in kidney cancer remains unknown. We have investigated the expression of MTSS1 in normal and malignant human kidney tissues and its molecular interaction within kidney cancer cells.


METHODS
The expression of MTSS1 in human kidney tissues and kidney cancer cell lines was assessed at both the mRNA and protein levels using RT-PCR and immunohistochemistry, respectively. Full-length MTSS1 cDNA expression vector was used to generate MTSS1 over-expressing cells. Effect of MTSS1 overexpression on cellular functions, was examined in kidney cancer cells of MTSS1 being over-expressed using a variety of in vitro assays. Involvement of Sonic Hedgehog (SHH) pathway was tested by using Shh small inhibitors.


RESULTS
Epithelial cells at proximal tubules of kidney tissues were stained positively for MTSS1, while the staining was weak or absent from cells at corpuscles and cancer cells of tumour tissues. Similarly, in kidney cancer cell lines, CAKI-2 and UMRC-2, expressed very low level of MTSS1. Over-expression of MTSS1 reduced the growth, invasion, adhesion and migration of kidney cell lines in vitro. Shh inhibitors diminished the inhibitory effect of MTSS1 on cell migration.


CONCLUSIONS
MTSS1 expression is reduced in human kidney cancer cells. MTSS1 levels are inversely correlated with the growth, invasion, adhesion and migration of kidney cancer cells in vitro. MTSS1 suppresses migration of kidney cancer cells via SHH pathway, and is a putative tumour suppressor of kidney cancer.
Cardiff University-Capital Medical University Joint Centre for Biomedical Research, UK.
Peng
P
Du
Lin
L
Ye
Han
H
Li
Yong
Y
Yang
Wen G
WG
Jiang
D017209:Apoptosis; D015153:Blotting, Western; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D005434:Flow Cytometry; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D014704:Veratrum Alkaloids / Q000494:pharmacology
D053823:Hedgehog Proteins; C486778:MTSS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C509239:SHH protein, human; D014704:Veratrum Alkaloids; C000541:cyclopamine