Diversity of the Origin of Cancer Stem Cells in Oral Squamous Cell Carcinoma and Its Clinical Implications

Oral squamous cell carcinoma (OSCC) histopathologically accounts for ≥90% of oral cancer. Many clinicopathological risk factors for OSCC have also been proposed, and postoperative therapy is recommended in guidelines based on cancer stage and other risk factors. However, even if the standard treatment is provided according to the guidelines, a few cases rapidly recur or show cervical and distant metastasis. In this review article, we focus on the diversity of the origin of OSCC. We also discuss cancer stem cells (CSCs) as a key player to explain the malignancy of OSCC. CSCs are a subset of cancer cells that occupy a very small portion of the cancer mass and have characteristics of stem cells. When gene abnormalities accumulate in somatic stem cells, those cells transform into CSCs. CSCs as the origin of cancer then autonomously grow and develop into cancer. The histopathological phenotype of cancer cells is determined by the original characteristics of the somatic stem cells and/or surrounding environment. OSCC may be divided into the following three categories with different malignancy based on the origin of CSCs: cancer from oral epithelial stem cell-derived CSCs, cancer from stem cells in salivary gland-derived CSCs, and cancer from bone marrow-derived stem cell-derived CSCs

Treatment of an Extensive Maxillary Cyst Using Nasal Airway and Balloon Catheter Devices

Introduction. Large maxillary cysts occasionally expand into the maxilla and erode the maxillary sinus and nasal cavity. The Caldwell-Luc procedure is the recommended treatment for large maxillary sinus cysts. However, it is hard to preserve the nasal space in the case of large maxillary sinus cysts that penetrate into the nasal cavity. Methods. A 22-year-old man who had large maxillary sinus cysts was referred to our department for a surgical treatment. After removing the cyst from the maxillary sinus using the Caldwell-Luc procedure, we used nasal airway and balloon catheter devices to preserve the space of the inferior nasal meatus and maxillary sinus. These devices were removed 10 days postoperatively. Insertion and removal of both devices were simple and painless. Findings. The nasal airway and balloon catheter devices were useful for performing maxillary sinus surgery to remove large cysts. Our method was satisfactorily safe and was an effective minimally invasive treatment that preserved the space of the inferior nasal meatus and maxillary sinus

Primary syphilis with a tongue ulcer mimicking tongue cancer: a case report

The main symptom in primary syphilis is a small, painless, sore or ulcer called a chancre on the penis, vagina, or around the anus, although chancres can sometimes appear in the mouth or on the lips, fingers, or buttocks. We present the case of a man in his early 60 s with a chief complaint of a painful tongue ulcer. An ulcerated, indurated, and hemorrhagic lesion (23 × 14 mm) was found on the ventral tongue surface, near the oral floor. Palpation identified several swollen, mobile, elastic cervical lymph nodes, with no tenderness. We initially diagnosed tongue cancer; however, during a subsequent detailed examination for a malignant tumor, including biopsy and obtaining additional history, his disease was finally identified as primary syphilis with multiple swollen cervical lymph nodes. Oral amoxicillin and probenecid were started, and after 14 days, there was partial reduction in the size of the submandibular lymph nodes and the ulcer on the left tongue margin. The number of patients with syphilis in Japan increased by eight times from 2012 to 2018. We suggest that dentists consider primary syphilis as a differential diagnosis for oral refractory ulcer with induration and obtain a detailed patient history

Paclitaxel Potentiates the Anticancer Effect of Cetuximab by Enhancing Antibody-Dependent Cellular Cytotoxicity on Oral Squamous Cell Carcinoma Cells In Vitro

Administration of cetuximab (C-mab) in combination with paclitaxel (PTX) has been used for patients with head and neck squamous cell carcinoma (SCC) clinically. In this study, we attempted to clarify the molecular mechanisms of the enhancing anticancer effect of C-mab combined with PTX on oral SCC cells in vitro. We used two oral SCC cells (HSC4, OSC19) and A431 cells. PTX alone inhibited cell growth in all cells in a concentration-dependent manner. C-mab alone inhibited the growth of A431 and OSC19 cells at low concentrations, but inhibited the growth of HSC4 cells very weakly, even at high concentrations. A combined effect of the two drugs was moderate on A431 cells, but slight on HSC4 and OSC19 cells. A low concentration of PTX enhanced the antibody-dependent cellular cytotoxicity (ADCC) induced by C-mab in all of the cells tested. PTX slightly enhanced the anticancer effect of C-mab in this ADCC model on A431 and HSC4 cells, and markedly enhanced the anticancer effect of C-mab on OSC19 cells. These results indicated that PTX potentiated the anticancer effect of C-mab through enhancing the ADCC in oral SCC cells

Research Data for Primary syphilis with a tongue ulcer mimicking tongue cancer: a case report

Research Data for Primary syphilis with a tongue ulcer mimicking tongue cancer: a case report by Chonji Fukumoto, Manabu Zama, Toshiki Hyodo, Ryo Shiraishi, Ryouta Kamimura, Shuma Yagisawa, Tomonori Hasegawa, Yuske Komiyama, Sayaka Izumi, Takahiro Wakui and Hitoshi Kawamata in Journal of International Medical Research</p

Lysophosphatidylcholine Acyltransferase1 Overexpression Promotes Oral Squamous Cell Carcinoma Progression via Enhanced Biosynthesis of Platelet-Activating Factor

<div><p>Background</p><p>The relevance of lysophosphatidylcholine acyltransferase1 (LPCAT1), a cytosolic enzyme in the remodeling pathway of phosphatidylcholine metabolism, in oral squamous cell carcinoma (OSCC) is unknown. We investigated LPCAT1 expression and its functional mechanism in OSCCs.</p><p>Methods</p><p>We analyzed LPCAT1 mRNA and protein expression levels in OSCC-derived cell lines. Immunohistochemistry was performed to identify correlations between LPCAT1 expression levels and primary OSCCs clinicopathological status. We established LPCAT1 knockdown models of the OSCC-derived cell lines (SAS, Ca9-22) for functional analysis and examined the association between LPCAT1 expression and the platelet-activating factor (PAF) concentration and PAF-receptor (PAFR) expression.</p><p>Results</p><p>LPCAT1 mRNA and protein were up-regulated significantly (p<0.05) in OSCC-derived cell lines compared with human normal oral keratinocytes. Immunohistochemistry showed significantly (p<0.05) elevated LPCAT1 expression in primary OSCCs compared with normal counterparts and a strong correlation between LPCAT1-positive OSCCs and tumoral size and regional lymph node metastasis. In LPCAT1 knockdown cells, cellular proliferation and invasiveness decreased significantly (p<0.05); cellular migration was inhibited compared with control cells. Down-regulation of LPCAT1 resulted in a decreased intercellular PAF concentration and PAFR expression.</p><p>Conclusion</p><p>LPCAT1 was overexpressed in OSCCs and correlated with cellular invasiveness and migration. LPCAT1 may contribute to tumoral growth and metastasis in oral cancer.</p></div

Effect of LPCAT1 knockdown on OSCC-derived cell lines.

<p>(<b>A, B</b>) Proliferation assay of shMock- and shLPCAT1-transfected cells (SAS- and Ca9–22-derived transfectants). To determine the effect of shLPCAT1 on cellular proliferation, shLPCAT1- and shMock-transfected cells were seeded in 6-cm dishes at a density of 1×10⁴ viable cells/well. Both transfected cells were counted on seven consecutive days. The cellular growth of shLPCAT1-transfected cells (SAS- and Ca9–22- derived transfectants) is inhibited significantly compared with the shMock-transfected cells after 5 days (120 hours). The results are expressed as the mean ±SEM of values from three assays. The asterisks indicate significant (*<i>p</i><0.05, Mann-Whitney <i>U</i> test) differences between the shLPCAT1- and shMock-transfected cells. (<b>C, D</b>) Migration assay of shMock- and shLPCAT1-transfected cells (SAS- and Ca9–22-derived transfectants). To evaluate the effect of LPCAT1 knockdown on migration, uniform wounds were made in confluent culture of the shLPCAT1- and shMock-transfected cells (SAS- and Ca9–22-derived transfectants) and the extent of closure was monitored visually every 3 hours for 24 hours. The mean value was calculated from data obtained from three separate chambers. The wound area was decreased significantly (*<i>p</i><0.05, Mann-Whitney <i>U</i> test) in the culture of shMock-transfected cells after 12 hours, whereas a gap remained in the shLPCAT1-transfected cells. (<b>E, F</b>) Invasiveness assay of shMock- and shLPCAT1-transfected cells (SAS- and Ca9–22-derived transfectants). To evaluate the effect of LPCAT1 knockdown on invasiveness, we seeded 2.5×10⁵ cells in the serum-free medium of a 0.8-μm polyethylene terephthalate membrane insert in a transwell apparatus and added serum-supplemented medium in the lower chamber as a chemoattractant. After incubation at 37°C for 48 hours, cells that penetrated through the pores were fixed, stained, and counted using a light microscope at ×100 magnification. The mean value was calculated from data obtained from three separate chambers. The number of shLPCAT1-transfected cells penetrating through the pores is decreased significantly (*<i>p</i><0.05, Mann-Whitney <i>U</i> test) compared with the shMock-transfected cells.</p

Establishment of shLPCAT1-transfected cells.

<p>(<b>A</b>) Expression of <i>LPCAT1</i> mRNA in shMock- and shLPCAT1-transfected cells (SAS- and Ca9–22-derived transfectants). <i>LPCAT1</i> mRNA expression in shLPCAT1-transfected cells is significantly (*<i>p</i><0.05, Mann-Whitney <i>U</i> test) lower than in the shMock-transfected cells. (<b>B</b>) Immunoblot analysis of LPCAT1 protein in shMock- and shLPCAT1-transfected cells (SAS- and Ca9–22-derived transfectants). The LPCAT1 protein expression in shLPCAT1-transfected cells is decreased markedly compared with the shMock-transfected cells.</p

Expression profiles of LPCAT1 in OSCC-derived cell lines and OSCC samples.

<p>(<b>A</b>) Quantification of <i>LPCAT1</i> mRNA levels in OSCC-derived cell lines by qRT-PCR analysis. To determine the mRNA expression status of <i>LPCAT1</i>, we performed qRT-PCR analysis using 9 OSCC-derived cell lines (HSC-2, HSC-3, HSC-4, Sa3, SAS, Ca9–22, KOSC2, HO-1-N-1, and HO-1-u-1), and HNOKs. <i>LPCAT1</i> mRNA is significantly up-regulated in the nine OSCC-derived cell lines compared with the HNOKs. The data are expressed as the mean ±SEM of values from three assays (*<i>p</i><0.05, Mann-Whitney <i>U</i> test). (<b>B</b>) Immunoblot analysis of LPCAT1 in the OSCC-derived cells lines and HNOKs. To investigate the protein expression status of LPCAT1, we performed immunoblot analysis in the same OSCC-derived cell lines and HNOKs. The LPCAT1 protein expression level is significantly up-regulated in all OSCC-derived cell lines compared with the HNOKs. Densitometric LPCAT1 protein data are normalized to the GAPDH protein levels. The values are expressed as a percentage of the HNOKs. (<b>C</b>) IHC of LPCAT1 on primary OSCC samples. Representative IHC results are shown for LPCAT1 protein in normal oral tissue (a, b) and primary OSCCs (c, d). The original magnifications are 100×(a, c), and 400×(b, d). Strong LPCAT1 immunoreactivity is detected in the primary OSCCs. (<b>D</b>) The status of LPCAT1 protein expression in primary OSCCs (n = 55) and the normal counterparts. The LPCAT1 IHC scores are calculated as follows: IHC score = 1×(number of weakly stained cells in the field) + 2×(number of moderately stained cells in the field) + 3×(number of intensely stained cells in the fields). The LPCAT1 IHC scores for normal oral tissues range from 0.5 to 68.5 and that of primary OSCCs range from 23.7 to 205.9. The LPCAT1 protein expression levels in OSCCs are significantly (*<i>p</i><0.01, Mann-Whitney <i>U</i> test) higher than those in normal oral tissues.</p