Highly sensitive detection of invasive lung cancer cells by novel antibody against amino-terminal domain of laminin γ2 chain.
The laminin γ2 chain, a subunit of laminin-332 (α3β3γ2), is a molecular marker for invasive cancer cells, but its pathological roles in tumor progression remain to be clarified. It was recently found that the most N-terminal, domain V (dV) of γ2 chain has activities to bind CD44 and stimulate tumor cell migration and vascular permeability. In the present study, we prepared a mAb recognizing γ2 dV. Immunoblotting with this antibody, for the first time, showed that proteolytic fragments containing dV in a range of 15-80 kDa were highly produced in various human cancer cell lines and lung cancer tissues. In immunohistochemistry of adenocarcinomas and squamous cell carcinomas of the lung, this antibody immunostained the cytoplasm of invasive tumor cells and adjacent stroma much more strongly than a widely used antibody recognizing the C-terminal core part of the processed γ2 chain. This suggests that the dV fragments are highly accumulated in tumor cells and stroma compared to the processed γ2 protein. The strong tumor cell staining with the dV antibody correlated with the tumor malignancy grade. We also found that the laminin β3 and α3 chains were frequently overexpressed in tumor cells and tumor stroma, respectively. The cytoplasmic dV detection was especially prominent in tumor cells infiltrating stroma, but low in the cells surrounded by basement membranes, suggesting that the active tumor-stroma interaction is critical for the aberrant γ2 expression. The present study suggests important roles of laminin γ2 N-terminal fragments in tumor progression.
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan.|Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Kaoru
K
Miyazaki
Department of Pathology, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Jun
J
Oyanagi
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan.
Atsuko
A
Sugino
Division of Cell Biology, Kihara Institute for Biological Research, Yokohama City University, Yokohama, Japan.
Hiroki
H
Sato
Department of Pathology, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Tomoyuki
T
Yokose
Department of Thoracic Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan.
Haruhiko
H
Nakayama
Molecular Pathology and Genetics Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Yohei
Y
Miyagi
D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D045744:Cell Line, Tumor; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000737:chemistry / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport
D000911:Antibodies, Monoclonal; D015415:Biomarkers; C400567:LAMC2 protein, human; D007797:Laminin
Biomarker; laminin γ2; lung cancer; monoclonal antibody; tumor invasion
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