Oncosuppressor-Mutated Cells as a Liquid Biopsy Test for Cancer-Screening

Mohamed Abdouh,Vincenzo Arena,Goffredo Orazio Arena,Zu-Hua Gao,Manuel Arena,Miguel N Burnier

doi:10.1038/s41598-019-38736-y

Abstract

We reported on the ability of immortalized or oncosuppressor-mutated cells (OMCs) to uptake circulating cancer-factors and give tumors when transplanted into mice. This led to the first biological based liquid biopsy test, which we called MATER-D platform. In the present study, we showed for the first time that a different type of OMCs (PTEN-deficient human epithelial MCF10A cells) turn malignant when exposed to cancer patient’s sera, confirming the concept that different cells with diverse oncosuppressor mutations can uptake cancer factors and be used in biological based liquid biopsy tests. Our observations were confirmed in a large variety of solid and haematological malignancies. This test was able to detect dysplasia and carcinomas in situ lesions in different organs and circulating factors in cancer patients years after the removal of their lesions. To our knowledge, this ability is unique and not shared by other liquid biopsy platforms. Immunohistochemistry analysis of the xenotransplants revealed identical patterns of differentiation regardless of the cancer type, showing that differentiation through horizontal transfer might be dependent on the nature of the target cells rather than the type of cancer factors. These data strengthen the notion that OMC-based liquid biopsy tests might be promising platforms for cancer screening.

Highlights

Horizontal transfer of molecules, which include signal proteins, bioactive lipids, and genetic material, through microvesicles or exosomes (EVs) is a recognized method of intercellular communication implemented in numerous physiological and pathological processes[1,2,3,4,5,6,7,8,9,10,11,12]
The ability of the oncosuppressor-mutated cells (OMCs) to “sense” neoplastic factors circulating in the serum, uptake them, turn into malignant cells and give cancer masses when transplanted into NOD-SCID mice was further investigated by our group to verify if this peculiar feature could be incorporated into a biological platform and be used as a liquid biopsy test for cancer screening
We aimed to verify if a different type of OMCs such as the human epithelial breast cell line MCF10A27,28 with a PTEN deletion was as effective in sensing oncogenic factors circulating in the sera of cancer patients as the OMCs we previously studied[18,19]

Summary

Introduction

Horizontal transfer of molecules, which include signal proteins, bioactive lipids, and genetic material, through microvesicles or exosomes (EVs) is a recognized method of intercellular communication implemented in numerous physiological and pathological processes[1,2,3,4,5,6,7,8,9,10,11,12]. We demonstrated that BRCA1-mutated fibroblasts turned into cancer cells, which exhibited phenotypical and immunohistochemical differentiation comparable to the cancer of the donor patients[18,19] These discoveries, for the first time, confirmed the legitimacy of the hypothesis that the metastatic process might be secondary to an horizontal transfer of malignant traits rather than to circulating cells. The ability of the OMCs to “sense” neoplastic factors circulating in the serum, uptake them, turn into malignant cells and give cancer masses when transplanted into NOD-SCID mice was further investigated by our group to verify if this peculiar feature could be incorporated into a biological platform and be used as a liquid biopsy test for cancer screening. We aimed to verify if a different type of OMCs such as the human epithelial breast cell line MCF10A27,28 with a PTEN deletion was as effective in sensing oncogenic factors circulating in the sera of cancer patients as the OMCs we previously studied[18,19]

Objectives

Methods

Results

Discussion

Conclusion