Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma.
BACKGROUND
Podoplanin, a mucin-type transmembrane glycoprotein, is thought to be one of the cancer stem cell markers for squamous-cell carcinoma of the vulva. The objectives of the present study were to examine the role of podoplanin in esophageal squamous-cell carcinoma (ESCC).


METHODS
Expression of podoplanin was examined immunohistochemically in 61 cases of ESCC that had not been treated with chemotherapy or radiotherapy before surgery. Because cancer stem-cell quantities have been reported to increase with chemotherapy and radiotherapy, cases in patients who did not receive such prior therapies were included in this study. Cases with >10% tumor cells showing signals for podoplanin were categorized as podoplanin high, and the others were classified as podoplanin low. The effects of podoplanin on the behavior of cancer cells were evaluated in ESCC cell lines in which podoplanin expression was knocked down.


RESULTS
To examine whether podoplanin could be used as a cancer stem cell marker for ESCC, podoplanin-positive and podoplanin-negative fractions were sorted separately from the ESCC cell line and cultured. Podoplanin-positive ESCC cells yielded both podoplanin-positive and podoplanin-negative cells, whereas few cells were obtained from podoplanin-negative ESCC cells. When podoplanin expression was knocked down, ESCC cell lines became vulnerable to anticancer drugs and showed defective invasion and tumorigenic activities. Nineteen (31.1%) of 61 cases were categorized as podoplanin high. Podoplanin-high cases were correlated with T category, stage of disease, lymphatic and vascular invasion, recurrence, and prognosis of patients. Podoplanin-low cases showed better overall and disease-free survival.


CONCLUSIONS
There is a role for podoplanin in tumorigenesis and malignant progression in ESCC.
Rahadiani
Nur
N
Department of Pathology, Osaka University, Graduate School of Medicine, Osaka, Japan.
Ikeda
Jun-ichiro
J
Makino
Tomoki
T
Tian
Tian
T
Qiu
Ying
Y
Mamat
Suhana
S
Wang
Yi
Y
Doki
Yuichiro
Y
Aozasa
Katsuyuki
K
Morii
Eiichi
E
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation / Q000187:drug effects; D003114:Colony-Forming Units Assay; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D046888:Tissue Array Analysis; D019772:Topotecan / Q000494:pharmacology; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000098853:Podoplanin
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D019772:Topotecan; C117468:PDPN protein, human; D000098853:Podoplanin