Project description:Metastasis formation is the major cause for cancer-related deaths and the underlying mechanisms remain poorly understood. In this study we describe spontaneous metastasis xenograft mouse models of human neuroblastoma used for unbiased identification of metastasis-related proteins by applying an infrared laser (IR) for sampling primary tumor and metastatic tissues, followed by mass spectrometric proteome analysis. IR aerosol samples were obtained from ovarian and liver metastases, which were indicated by bioluminescence imaging (BLI), and matched subcutaneous primary tumors. Corresponding histology proved the human origin of metastatic lesions. Ovarian metastases were commonly larger than liver metastases indicating differential outgrowth capacities. Among ~1,900 proteins identified at each of the three sites, 55 proteins were differentially regulated in ovarian metastases while 312 proteins were regulated in liver metastases. There was an overlap of 21 and 7 proteins up- and down-regulated at both metastatic sites, respectively, most of which were so far not related to metastasis such as LYPLA2, EIF4B, DPY30, LGALS7, PRPH, and NEFM. Moreover, we established in vitro sublines from primary tumor and metastases and demonstrate differences in cellular protrusions, migratory/invasive potential and glycosylation. Summarized, this work identified several novel putative drivers of metastasis formation that are tempting candidates for future functional studies.

| S-EPMC6143537 | biostudies-literature

Organoid in colorectal cancer: progress and challenges.

Project description:Patient-derived tumor organoids (PDOs) currently represent important modeling tools in pre-clinical investigation of malignancies. Organoid cultures conserve the genetic and phenotypic characteristics of the original tumor and maintain its heterogeneity, allowing their application in many research fields. PDOs derived from colorectal cancer (CRC) have been used for genetic modeling to investigate the function of driver genes. Some researchers have been exploring the value of CRC PDOs in chemotherapy, targeted therapy, and radiotherapy response prediction. The successful generation of PDOs derived from CRC could deepen our understanding of CRC biology and provide novel tools for cancer modeling, for realizing precision medicine by assessing specimens from individual patients ex vivo. The present review discusses recently reported advances in CRC PDOs and the challenges they face as pre-clinical models in CRC research.

| S-EPMC7462208 | biostudies-literature

Single-cell sequencing of colorectal cancer liver metastases

Project description:Cancer cells and fibroblasts from 6 metastases obtained from 5 different patients were submitted to single-cell sequencing on the 10xGenomics platform. These data revealed different subpopulations of cancer-associated fibroblasts (CAF) and their ligand-receptor interactions with cancer cells.

2022-11-07 | GSE158692 | GEO

Fisetin suppresses colorectal cancer growth through AKAP12 in the patient-derived organoid xenograft model

Project description:To investigate the genetic changes induced by fisetin treatment, we established a patient-derived organoid xenograft model (PDOX) of the control group and the group treated with fisetin 200mpk. We then performed gene expression profiling analysis using data from RNA-seq from both groups.

2023-10-10 | GSE213963 | GEO

Origins of lymphatic and distant metastases in human colorectal cancer.

Project description:The spread of cancer cells from primary tumors to regional lymph nodes is often associated with reduced survival. One prevailing model to explain this association posits that fatal, distant metastases are seeded by lymph node metastases. This view provides a mechanistic basis for the TNM staging system and is the rationale for surgical resection of tumor-draining lymph nodes. Here we examine the evolutionary relationship between primary tumor, lymph node, and distant metastases in human colorectal cancer. Studying 213 archival biopsy samples from 17 patients, we used somatic variants in hypermutable DNA regions to reconstruct high-confidence phylogenetic trees. We found that in 65% of cases, lymphatic and distant metastases arose from independent subclones in the primary tumor, whereas in 35% of cases they shared common subclonal origin. Therefore, two different lineage relationships between lymphatic and distant metastases exist in colorectal cancer.

| S-EPMC5536201 | biostudies-literature

Human primary and metastatic colorectal cancer (CRC) samples

Project description:Data Access Committee EGAC00001002954

| EGAC00001002954 | EGA