A lymph node metastatic mouse model reveals alterations of metastasis‐related gene expression in metastatic human oral carcinoma sublines selected from a poorly metastatic parental cell line

Zhang, Xin; Liu, Yanna; Gilcrease, Michael Z.; Yuan, Xingliang; Clayman, D.D.S. Gary L.; Adler‐Storthz, Karen; Chen, Zhuo

doi:10.1002/cncr.10837

Cited by 73 publications

(81 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…By using these cell lines, we observed that PAR-1 was significantly down-regulated in the selected highly metastatic cell lines as compared with their poorly metastatic parental cell line (24). Our current study complements this previous work by extending PAR-1 expression studies to human tumor tissues.…”

Section: Introductionsupporting

confidence: 77%

“…To test this hypothesis, we initially examined the expression of the differentiation marker, involucrin, in the highly metastatic cell lines 686LN-M3a3 and 686LN-M3b3 established from the lymph node metastasis mouse model. These cell lines expressed lower PAR-1 than their poorly metastatic parental cell line 686LN (24). We found that the expression of involucrin was significantly down-regulated in highly metastatic cell lines as compared with 686LN (Fig.…”

Section: Correlation Of Par-1 Expression With a Differentiationmentioning

confidence: 68%

“…They were kindly provided by Dr. Peter G. Sacks (New York University College of Dentistry, New York, NY). 686LN-M3a2, 686LN-M3a3, 686LN-M3b2, and 686LN-M3b3 are highly metastatic cell lines generated by in vivo selection from 686LN that has low metastatic potential in the lymph node of nude mouse as described previously (24). SCCHN cell lines Tu212 and 886LN were established from a primary hypopharynx tumor and cervical lymph node metastases from a laryngeal primary tumor, respectively, from the University of Texas M.D.…”

Section: Methodsmentioning

confidence: 99%

“…Northern blotting was performed using the method described previously (24). In brief, mRNA was prepared using the Oligotex mRNA Purification kit (Qiagen, Valencia, CA) from par-1 cDNA-transfected cell lines.…”

Section: Methodsmentioning

confidence: 99%

“…To study metastasis of SCCHN, we previously established highly metastatic SCCHN cell lines from a rarely metastatic SCCHN cell line through in vivo selection using a mouse model of lymph node metastasis of human tumors (24,25). By using these cell lines, we observed that PAR-1 was significantly down-regulated in the selected highly metastatic cell lines as compared with their poorly metastatic parental cell line (24).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Correlation of Protease-Activated Receptor-1 With Differentiation Markers in Squamous Cell Carcinoma of the Head and Neck and Its Implication in Lymph Node Metastasis

Zhang

Hunt²,

Landsittel

et al. 2004

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: Protease-activated receptor-1 (PAR-1) is a Gprotein-coupled receptor that contributes to multiple signal transduction pathways. Although the functions of PAR-1 in many normal cells, such as platelets and astrocytes, have been well studied, its roles in cancer progression and metastasis have not been fully elucidated, and studies to date appear contradictory.Experimental Design: To clarify the function of PAR-1 in metastasis of squamous cell carcinoma of the head and neck (SCCHN), we examined PAR-1 expression in clinical specimens by immunohistochemistry and in SCCHN cell lines by immunoblotting. Furthermore, par-1 cDNA-transfected SCCHN cell lines were also used to verify PAR-1-mediated pathway.Results: The metastatic tumors showed a lower percentage of PAR-1-positive cells (46%) and lower levels of PAR-1 expression (median weight index ‫؍‬ 10) than node negative primary tumors (80% and median weight index ‫؍‬ 60, respectively). In addition, expression level of PAR-1 positively correlated with levels of keratinocyte differentiation markers keratin-1, -10, and -11. Additional studies using sense and antisense par-1 cDNA-transfected SCCHN cell lines illustrated that the presence of PAR-1 was required for the expression of involucrin, a keratinocyte differentiation marker. PAR-1 expression also contributes to activation of the mitogen-activated protein kinase (MAPK) pathway. Blocking MAPK activation by a mitogen-activated protein/ extracellular signal-regulated kinase inhibitor, not by a phosphatidylinositol 3 -kinase inhibitor, reduced level of involucrin, suggesting that regulation of involucrin by PAR-1 is partially through the MAPK signaling pathway.Conclusions: Our study suggests that PAR-1 signaling induces differentiation markers in SCCHN cells, and its expression is conversely correlated with cervical lymph node metastasis.

show abstract

Section: Introductionsupporting

confidence: 77%

Section: Correlation Of Par-1 Expression With a Differentiationmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Correlation of Protease-Activated Receptor-1 With Differentiation Markers in Squamous Cell Carcinoma of the Head and Neck and Its Implication in Lymph Node Metastasis

Zhang

Hunt²,

Landsittel

et al. 2004

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

On‐chip integrated labelling, transport and detection of tumour cells

et al. 2011

View full text Add to dashboard Cite

Microflow cytometry represents a promising tool for the investigation of diagnostic and prognostic cellular cancer markers, particularly if integrated within a device that allows primary cells to be freshly isolated from the solid tumour biopsies that more accurately reflect patient-specific in vivo tissue microenvironments at the time of staining. However, current tissue processing techniques involve several sequential stages with concomitant cell losses, and as such are inappropriate for use with small biopsies. Accordingly, we present a simple method for combined antibody-labelling and dissociation of heterogeneous cells from a tumour mass, which reduces the number of processing steps. Perfusion of ex vivo tissue at 4°C with antibodies and enzymes slows cellular activity while allowing sufficient time for the diffusion of minimally active enzymes. In situ antibody-labelled cells are then dissociated at 37°C from the tumour mass, whereupon hydrogel-filled channels allow the release of relatively low cell numbers (<1000) into a biomimetic microenvironment. This novel approach to sample processing is then further integrated with hydrogel-based electrokinetic transport of the freshly liberated fluorescent cells for downstream detection. It is anticipated that this integrated microfluidic methodology will have wide-ranging biomedical and clinical applications.

show abstract