Early postoperative epidermal growth factor receptor inhibition: Safety and effectiveness in inhibiting microscopic residual of oral squamous cell carcinoma in vivo

Sano, Daisuke; Gule, Maria K.; Rosenthal, David I.; Bell, Diana; Yates, J. M.; El‐Naggar, Adel K.; Myers, Jeffrey N.

doi:10.1002/hed.22961

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…The unfavorable clinical outcome is closely associated with its high lymphatic and local metastatic potential 4 . Thus far, decisions regarding the elective and therapeutic management of lymphatic metastases are made mainly on clinical grounds, which are not very precise because we cannot make predictions from the size and extent of invasion of the primary tumors 5 . Therefore, new biomarkers are needed to refine which subtype of primary OSCC is of high metastatic character, and could be tremendously beneficial regarding how to manage OSCC in the clinic.…”

Section: Introductionmentioning

confidence: 99%

Phosphoglycerate Mutase 1 Predicts the Poor Prognosis of Oral Squamous Cell Carcinoma and is Associated with Cell Migration

Zhang¹,

Wu²,

Zhang³

et al. 2017

J. Cancer

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Oral squamous cell carcinoma (OSCC) is a common malignant tumor with high metastatic potential. However, no good biomarker has been identified to refine which subtype is of high metastatic potential to make decisions regarding the elective and therapeutic management of lymphatic metastases. In this study, we investigated the role of the metabolic enzyme phosphoglycerate mutase 1 (PGAM1) in OSCC. PGAM1 expression was examined in tissue samples of 122 OSCC patients using immunohistochemistry, and the correlation between clinicopathological expression and PGAM1 expression was determined. Survival curves were generated using the Kaplan-Meier method, and multivariate analysis was performed by the Cox proportional hazards model. Moreover, PGAM1 was knocked down in the OSCC cell lines Cal27 and HN12, followed by determination of the change in cell migration and signaling pathways. PGAM1 expression is correlated with age, lymphatic metastasis and tumor recurrence and is closely associated with poor overall survival (OS) and disease-free survival (DFS). Intriguingly, PGAM1 is an independent risk factor for OS and DFS. After knocking down PGAM1 in Cal27 and HN12 cells, cell migration was remarkably decreased along with signaling pathway molecules, such as proto-oncogene c-SRC (SRC), Focal adhesion kinase (FAK) and Paxillin. The effect on cell migration was abolished following pretreatment with an SRC inhibitor. This study suggested that PGAM1 is a poor prognostic biomarker of OSCC and may be used to select patients of high metastatic potential in the clinic, and PGAM1 promotes the migration of OSCC cells is associated with the SRC pathway.

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Section: Introductionmentioning

confidence: 99%

Phosphoglycerate Mutase 1 Predicts the Poor Prognosis of Oral Squamous Cell Carcinoma and is Associated with Cell Migration

Zhang¹,

Wu²,

Zhang³

et al. 2017

J. Cancer

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“…Although the dissection of the primary tumor is beneficial, it may disturb metastatic homeostasis [ 9 ], resulting in the activation and rapid growth of latent tumors in distant organ, which has been suggested in several cancer types including breast, lung and head and neck cancers [ 10 – 12 ]. Due to being inspired by above papers and a model that has been proposed to explain the recurrence of breast cancer in a patient after surgical resection of the tumor [ 13 ], we wonder if removal of tumor-bearing lymph node (LN) may accelerate the occurrence of cancer metastasis.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes

et al. 2018

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BackgroundSurgical removal of primary tumors can promote the incidence of tumor metastasis. However, molecular mechanisms underlying this process remain unclear.MethodsWe inoculated tumor cells expressing luciferase gene into subiliac lymph node (SiLN) of the MXH10/Mo-lpr/lpr mice. The tumor-bearing SiLNs were surgically removed at a certain period of time after inoculation.ResultsIn vivo bioluminescence imaging system and histological staining revealed metastasis in lung, proper axillary lymph node (PALN) and liver. The lung metastasis rate in SiLN removal groups was significantly higher than in the control group using Fisher exact test. Mann-Whitney U-test indicated that the luciferase-positive tumor cells in the lung and liver were significantly higher than in the control groups. The lung samples in SiLN removal groups had strong expression of lysine oxidase (LOX). Moreover, the number of CD11b+ cells in the lung and liver in the SiLN removal groups was significantly increased, which was positively correlated with LOX expression level. In addition, the condition of LOX and CD11b in liver was similar to lung. In the SiLN surgical removal groups, the matrix metalloproteinase (MMP)-2 and VEGFA expression in the lung tissues was significantly higher than in the control groups; the collagen fibers per area around the pulmonary vessels was quite significantly lower and negatively correlated with the expression of MMP-2 by Spearman’s analysis. Our data indicated that the reticular fibers were deposited and disordered in the tumor tissues of the lungs in the removal groups, and the reticular fibers per area was higher than in the control groups. The tumor cells in the PALN of control groups were significantly higher than in the SiLN removal groups, and CD169+ and CD11c+ cells were also higher than in the SiLN removal groups.ConclusionsAltogether, surgical removal of the tumor-bearing lymph node promoted tumor metastasis through changing the niche in lung and liver. Treatment targeting the metastatic niche might be an effective strategy to prevent tumor metastasis, thereby possibly increasing the survival and reducing the incidence of metastasis in cancer patients.

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“…The EGFR pathway modulates cancer proliferation and metastasis and cancer survival. Sano et al (52) previously postulated that the reason for local-regional failure of oral squamous cell carcinoma may be due to the activation of the EGFR pathway in residual cancer cells during wound healing. Hence, the administration of an anti-EGFR monoclonal antibody such as cetuximab may be valuable.…”

Section: Discussionmentioning

confidence: 99%

Wound fluid enhances cancer cell proliferation via activation of STAT3 signal pathway in vitro

et al. 2019

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Wound healing begins immediately after surgery with a modification of the microenvironment via a well-orchestrated interaction between cells, cytokines and growth factors. Some of these growth factors and cytokines have mitogenic effects on cancer cells, which may lead to enhanced cancer cell proliferation and early metastatic events. The present study aimed to investigate the effects of wound fluid (WF) on the head and neck squamous carcinoma cell lines FaDu and HLaC78 in vitro. WF was harvested from 7 patients who had undergone a planned neck dissection. The presence of cytokines and growth factors was evaluated with the dot blot assay. Proliferation and cell viability were investigated via MTT assay and Ki-67 staining. Cell invasion was measured via tree-dimensional invasion assay. Western blotting was used to investigate STAT 3 activation. WF contained several cytokines and growth factors responsible for pro-and anti-inflammation, chemotaxis, proliferation and angiogenesis. The proliferation effect of WF on FaDu and HLaC78 was concentration dependent. Media with 40% WF resulted in the highest proliferation effect. FaDu and HLaC78 exhibited enhanced motility after cultivation with 40% WF compared with cultivation with expansion medium. Cultivating cancer cells with WF had no advantageous effect on cell viability after the paclitaxel treatment. Western blot analysis revealed enhanced activation of the STAT3 signaling pathway by WF in both FaDu and HLaC78. In conclusion, surgery leads to excessive release of mitogenic factors. The contact of non-resected cancer cells and these factors may have a negative impact on patient outcome. Future investigations should specifically focus on the inhibition of mitogenic factors following cancer surgery in order to prevent early metastasis and cancer recurrence.

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Early postoperative epidermal growth factor receptor inhibition: Safety and effectiveness in inhibiting microscopic residual of oral squamous cell carcinoma in vivo

Cited by 12 publications

References 35 publications

Phosphoglycerate Mutase 1 Predicts the Poor Prognosis of Oral Squamous Cell Carcinoma and is Associated with Cell Migration

Phosphoglycerate Mutase 1 Predicts the Poor Prognosis of Oral Squamous Cell Carcinoma and is Associated with Cell Migration

Evaluation of metastatic niches in distant organs after surgical removal of tumor-bearing lymph nodes

Wound fluid enhances cancer cell proliferation via activation of STAT3 signal pathway in vitro

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