KR-102962998-B1 - Lung cancer modeling using normal alveolar organoids with lung cancer cells

Abstract

The present invention relates to a lung cancer model based on a normal lung organoid prepared by fusing cancer cells into a normal lung organoid. This model allows for the observation of the progression or metastasis of lung cancer from the early stages of cell proliferation to the stage where the tumor takes shape, and also enables the comparison of the effects of anticancer drugs at each stage, thereby providing information on appropriate treatments according to the stage of cancer development. Furthermore, since the lung cancer model according to the present invention is in the form of a fusion of normal lung organoids and cancer cells, it can be usefully utilized to verify the effects of anticancer drugs on normal tissues and cancer cell-specific apoptosis effects. In addition, since conventional methods of injecting human lung cancer cells into mice had the problem of causing unpredictable reactions due to immune responses, it is expected that this model can be usefully utilized as a human lung cancer development model.

Inventors

• 김성원
• 조아영
• 임민재
• 이정은
• 양승호

Assignees

• 가톨릭대학교 산학협력단

Dates

Publication Date

20260511

Application Date

20230530

Priority Date

20220628

Claims (12)

1. A method for preparing a lung cancer model using a normal lung organoid, comprising the step of co-cultured normal lung organoids and lung cancer cells.
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3. In paragraph 1, A method for preparing a lung cancer model, characterized in that the lung cancer cells are human primary cancer cells or established cancer cells.
4. In paragraph 3, A method for preparing a lung cancer model, characterized in that the established cancer cells are H1299 cells.
5. In paragraph 1, A method for preparing a lung cancer model, characterized in that the normal lung organoid and lung cancer cells are mixed in a cell ratio of 1:1 to 100.
6. In paragraph 1, A method for manufacturing a lung cancer model, characterized by further including the step of mixing normal lung organoids and lung cancer cells and centrifuging them before co-culture.
7. A lung cancer model produced by the manufacturing method of any one of claims 1, and 3 to 6.
8. In Paragraph 7, A lung cancer model characterized in that the above lung cancer is primary lung cancer or metastatic lung cancer.
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Description

Lung cancer modeling using normal alveolar organoids with lung cancer cells The present invention relates to an organoid system capable of providing a lung cancer model based on a lung organoid prepared by fusing lung cancer cells to a normal lung organoid, and its uses, etc. Currently, animal models are widely used for disease modeling; however, because animals differ from humans in physiological aspects, there are limitations in replicating actual human diseases in animals, and ethical issues continue to arise. Organoids are three-dimensional cellular structures composed of various cells that make up tissues, and they have recently garnered attention for their ability to mimic the in vivo environment. Consequently, they are being actively researched and utilized across various fields, ranging from basic biology research to diverse applied research areas such as new drug development, disease modeling, and regenerative therapy. In particular, organoid models are gaining attention because they enable research into disease mechanisms and personalized diagnosis. Meanwhile, lung diseases caused by genetic factors, excessive smoking, and fine dust, viruses, and bacteria resulting from air pollution are one of the leading causes of death worldwide. However, due to the lack of disease models, research into the mechanisms of lung diseases is difficult, and the development of treatments is also very challenging. Therefore, there is an urgent need to develop in vitro models of lung diseases that can precisely simulate human lung diseases. Figures 1 to 3 each show a lung cancer model prepared by fusing lung cancer cells into a normal lung organoid derived from a different person. Figure 4 is a diagram showing the results of confirming the expression of alveolar-specific markers HT1-56, HT2-280, and ColA1 in a lung cancer model prepared by fusing lung cancer cells into normal lung organoids. Each description and embodiment disclosed in the present invention may be applied to each other description and embodiment. That is, all combinations of the various elements disclosed in the present invention fall within the scope of the present invention. Furthermore, the scope of the present invention should not be considered limited by the specific descriptions provided below. Furthermore, terms not specifically defined in this specification should be understood to have the meanings commonly used in the technical field to which the present invention pertains. Additionally, unless specifically defined in the context, the singular includes the plural, and the plural includes the singular. The inventors conducted extensive research to develop an in vitro lung cancer model capable of verifying the progression and metastasis processes of lung cancer and the effects of anticancer drugs. As a result, they completed the present invention by constructing a lung cancer model based on a normal lung organoid through the fusion of various cancer cells, including lung cancer cells, with a normal lung organoid. The present invention will be described in detail below. The present invention provides a method for preparing a lung cancer model using a normal lung organoid, comprising the step of co-cultured a normal lung organoid and cancer cells. In addition, the present invention provides, in another aspect of the present invention, a lung cancer model produced by the method for producing the lung cancer model. In the present invention, the term “lung cancer model” refers to a lung cancer model in which cancer cells are fused to a normal lung organoid, and which allows for the observation of the progression of cancer from the early stages until tumor formation or the metastasis of non-lung cancer to the lungs, depending on the type of cancer cells combined. In the present invention, the term "organoid" refers to a cell aggregate created by re-aggregating and recombining cells isolated from stem cells or organ-derived cells using a 3D culture method, and may include an organoid or cell cluster formed from a suspension cell culture. The organoid may also be referred to as a small organoid, an organ analog, or an organoid. Specifically, the organoid comprises one or more types of cells among the various types of cells constituting an organ or tissue, and must be capable of reproducing the form and function of the tissue or organ. According to one embodiment of the present invention, the lung organoid may be manufactured using type 2 alveolar cells isolated from lung tissue, but is not limited thereto, and the lung tissue may be derived from a human who is not cancerous. In the present invention, “normal” refers to a state that is not a malignant tumor or cancer (Negative for malignancy, negative for malignant tumor cells), and includes a completely normal state free of any disease, as well as a state corresponding to a disease state other than a malignant tumor (cancer). In the present invention, the cancer may be one or more selected from the grou