In vivo selection of highly metastatic human ovarian cancer sublines reveals role for AMIGO2 in intra-peritoneal metastatic regulation

Liu, Yueying; Yang, Jing; Shi, Zonggao; Tan, Xuejuan; Jin, Norman; O'Brien, C; Ott, Connor; Grisoli, Anna; Lee, Eric B.; Volk, Kelly; Conroy, Meghan; Franz, Emily; Bryant, Annamarie T.; Campbell, Leigh; Crowley, Brian J.; Grisoli, Stephen; Alexandrou, Aris T.; Li, Chunyan; Harper, Elizabeth I.; Asem, Marwa; Johnson, Jeff J.; Léonard, A; Santanello, Katie; Klein, Ashley; Wang, Qingfei; Zhang, Siyuan; Hilliard, Tyvette S.; Stack, M. Sharon

doi:10.1016/j.canlet.2021.01.024

Cited by 20 publications

(17 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, MSLN expression does regulate MCA size, as mesothelial cells that express MSLN produce larger MCAs when co-cultured with ovarian cancer cells. As shown by others, MCA compactness is evident of a more aggressive and invasive subpopulation of ovarian tumor cells [41][42][43]. Differences in MCA size were observed in human ascitic fluid and may be the result of detachment or the preservation of proliferation from the primary tumor [41].…”

Section: Discussionmentioning

confidence: 56%

“…Isolated MSLN WT and MSLN KO mesothelial cells were stained with CMFDA CellTracker dye and combined 1:1 (300 cells) with the mouse ovarian surface epithelial ID8-RFP tagged cells. As previously described, droplets (20 µL) were plated on the inner surface of a 150 × 25 mm tissue culture dish lid with phosphate-buffered saline in the lower dish [43,59]. Parallel monocultures of MSLN WT and MSLN KO mesothelial cells or mouse ovarian ID8-RFP cells were prepared as a control.…”

Section: Multicellular Aggregate Hanging Drop Culturementioning

confidence: 99%

See 1 more Smart Citation

Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

Hilliard

Kowalski

Iwamoto

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

Mesothelin (MSLN), a glycoprotein normally expressed by mesothelial cells, is overexpressed in ovarian cancer (OvCa) suggesting a role in tumor progression, although the biological function is not fully understood. OvCa has a high mortality rate due to diagnosis at advanced stage disease with intraperitoneal metastasis. Tumor cells detach from the primary tumor as single cells or multicellular aggregates (MCAs) and attach to the mesothelium of organs within the peritoneal cavity producing widely disseminated secondary lesions. To investigate the role of host MSLN in the peritoneal cavity we used a mouse model with a null mutation in the MSLN gene (MSLNKO). The deletion of host MSLN expression modified the peritoneal ultrastructure resulting in abnormal mesothelial cell surface architecture and altered omental collagen fibril organization. Co-culture of murine OvCa cells with primary mesothelial cells regardless of MSLN expression formed compact MCAs. However, co-culture with MSLNKO mesothelial cells resulted in smaller MCAs. An allograft tumor study, using wild-type mice (MSLNWT) or MSLNKO mice injected intraperitoneally with murine OvCa cells demonstrated a significant decrease in peritoneal metastatic tumor burden in MSLNKO mice compared to MSLNWT mice. Together, these data support a role for host MSLN in the progression of OvCa metastasis.

show abstract

Section: Discussionmentioning

confidence: 56%

Section: Multicellular Aggregate Hanging Drop Culturementioning

confidence: 99%

Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

Hilliard

Kowalski

Iwamoto

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our method can be used to evaluate the volume of disseminated tumors and investigate spatial location-speci c cancer development mechanisms. To date, evaluation of the volume of disseminated tumors has mainly been based on the macroscopic examination of resected specimens or in vivo uorescence imaging [31][32][33]. Our method offers de nite advantages over those two techniques; compared to macroscopic examination, our approach enables screening of the entire peritoneal cavity without overlooking small tumor nodules and does not require consideration of attenuation or irregular uorescence due to the imaging conditions.…”

Section: Discussionmentioning

confidence: 99%

A Practical Spatial Analysis Method for Elucidating the Biological Mechanisms of Disseminated Cancers in Vivo

Ota

Sato

Yoshihara

et al. 2022

Preprint

View full text Add to dashboard Cite

The elucidation of spatial interactions between cancer and host cells is important for the development of new therapies against disseminated cancers. In this study, we developed a practical spatial analysis method using a gel-based embedding system and applied it to a murine model of cancer dissemination. After euthanization, every abdominal organ enclosed in the peritoneum was extracted en bloc. We injected agarose gel into the peritoneal cavities to preserve the spatial locations of organs including metastatic niches, then produced specimens after the gel was solidified. Preservation of the original spatial localization was confirmed by comparing the magnetic resonance imaging results to the sectioned specimens. We examined the effects of spatial localization on cancer hypoxia using hypoxia markers immunohistochemically. Finally, we identified the mRNA expression on the specimens and demonstrated the applicability of spatial genetic analysis. In conclusion, we established a practical method for the in vivo investigation of spatial location-specific biological mechanisms on disseminated cancers.

show abstract

“…Wang et al (2017) recently reported that CTGF might promote osteosarcoma angiogenesis and metastasis by upregulating expression of Angpt2, consistent with our finding that CTGF is upregulated in metastatic osteosarcoma and is pro-metastatic. AMIGO2 (adhesion molecule with Ig-like domain 2) is a transmembrane protein with known oncoprotein function that is described as a driver of metastasis in breast and ovarian cancer and metastatic melanoma (Fontanals-Cirera et al, 2017;Sonzogni et al, 2018;Liu et al, 2021). The prolactin regulatory element binding (PREB) gene encodes a transcription factor that regulates target genes by binding to the prolactin gene (PRL) promoter (Zhang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

A Novel Six Metastasis-Related Prognostic Gene Signature for Patients With Osteosarcoma

Zheng

Xia

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Osteosarcoma is the most common malignant bone tumor, and although there has been significant progress in its management, metastases often herald incurable disease. Here we defined genes differentially expressed between primary and metastatic osteosarcoma as metastasis-related genes (MRGs) and used them to construct a novel six-MRG prognostic signature for overall survival of patients with osteosarcoma. Validation in internal and external datasets confirmed satisfactory accuracy and generalizability of the prognostic model, and a nomogram based on the signature and clinical variables was constructed to aid clinical decision-making. Of the six MRGs, FHIT is a well-documented tumor suppressor gene that is poorly defined in osteosarcoma. Consistent with tumor suppressor function, FHIT was downregulated in osteosarcoma cells and human osteosarcoma samples. FHIT overexpression inhibited osteosarcoma proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, FHIT overexpression upregulate the epithelial marker E-cadherin while repressing the mesenchymal markers N-cadherin and vimentin. Our six-MRG signature represents a novel and clinically useful prognostic biomarker for patients with osteosarcoma, and FHIT might represent a therapeutic target by reversing epithelial to mesenchymal transition.

show abstract

In vivo selection of highly metastatic human ovarian cancer sublines reveals role for AMIGO2 in intra-peritoneal metastatic regulation

Cited by 20 publications

References 53 publications

Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

Host Mesothelin Expression Increases Ovarian Cancer Metastasis in the Peritoneal Microenvironment

A Practical Spatial Analysis Method for Elucidating the Biological Mechanisms of Disseminated Cancers in Vivo

A Novel Six Metastasis-Related Prognostic Gene Signature for Patients With Osteosarcoma

Contact Info

Product

Resources

About