ABSTRACT: Intra-tumoral heterogeneity in metastatic potential and survival signaling between iso-clonal HCT116 and HCT116b human colon carcinoma cell lines
Project description:Characterization of the intra-tumoral heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS). Microarray analysis revealed an upregulation of survival and metastatic genes in the highly metastatic HCT116 primary colon tumor cells compared to the poorly metastatic HCT116b primary colon tumor cells.
Project description:Characterization of the intra-tumoral heterogeneity between two iso-clonal human colon cancer sublines HCT116 and HCT116b on their ability to undergo metastatic colonization and survive under growth factor deprivation stress (GFDS). Microarray analysis revealed an upregulation of survival and metastatic genes in the highly metastatic HCT116 primary colon tumor cells compared to the poorly metastatic HCT116b primary colon tumor cells. Total RNA obtained from isolated primary colon tumors of HCT116 and HCT116b xenograft transplanted animals obtained using the orthotopic implantation of HCT116 and HCT116b human colon cancer xenografts in the cecum of male athymic BALB/c nude mice were compared at their gene expression level.
Project description:Almost half of all patients diagnosed with colorectal cancer develop liver metastases. The potential role of intra-individual metastatic heterogeneity remains poorly characterized. By high-resolution DNA copy number analyses and a novel approach based on pair-wise genetic distance, we examined the genetic heterogeneity among multiple liver metastatic deposits obtained from 45 patients subject to curative liver resection. We found large variation in intra-individual metastatic heterogeneity. A high level of heterogeneity was associated with poor patient survival. Patients with metachronous metastases who received chemotherapy had significantly more heterogeneity than chemonaïve patients.
Project description:Deciphering intra- and inter-tumoral heterogeneity is essential for understanding gastric cancer (GC) biology and identifying effective therapeutic targets. We used single-cell RNA sequencing (scRNA-seq) to reveal the transcriptional heterogeneity of diverse cells within primary and metastatic GC and their roles in disease progression.
Project description:Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intra-tumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 mPC patients. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intra-patient, inter-tumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.
Project description:Metastatic prostate cancer (mPC) is a clinically and molecularly heterogeneous disease. While there is increasing recognition of diverse tumor phenotypes across patients, less is known about the molecular and phenotypic heterogeneity present within an individual. In this study, we aimed to define the patterns, extent, and consequences of inter- and intra-tumoral heterogeneity in lethal prostate cancer. By combining and integrating in situ tissue-based and sequencing approaches, we analyzed over 630 tumor samples from 52 mPC patients. Our efforts revealed phenotypic heterogeneity at the patient, metastasis, and cellular levels. We observed that intra-patient, inter-tumoral molecular subtype heterogeneity was common in mPC and showed associations with genomic and clinical features. Additionally, cellular proliferation rates varied within a given patient across molecular subtypes and anatomic sites. Single-cell sequencing studies revealed features of morphologically and molecularly divergent tumor cell populations within a single metastatic site. These data provide a deeper insight into the complex patterns of tumoral heterogeneity in mPC with implications for clinical management and the future development of diagnostic and therapeutic approaches.
Project description:We have assessed clonal heterogeneity within individual primary tumours and metastasis and also during the distinct stages of malignant tumour progression using the Confetti lineage reporter in the background of the MMTV-PyMT mouse model of metastatic breast cancer. Comparative gene expression analysis of the clonal populations reveals a substantial level of heterogeneity across and also within the various stages of breast carcinogenesis. This intra-stage heterogeneity is manifested by differences in cell proliferation, where the fast-proliferating subclass is further enriched in oxidative phosphorylation and cell death.
