Interstitial serum albumin empowers osteosarcoma cells with FAIM2 transcription to obtain viability via dedifferentiation
Adult
Male
0301 basic medicine
Mice, Inbred BALB C
Osteosarcoma
0303 health sciences
Adolescent
Cell Survival
Membrane Proteins
Mice, Nude
Cell Dedifferentiation
Middle Aged
3. Good health
03 medical and health sciences
Cell Line, Tumor
Animals
Humans
Female
Calcium Channels
Calcium Signaling
Apoptosis Regulatory Proteins
Child
Cytoskeleton
Serum Albumin
DOI:
10.1007/s11626-019-00421-9
Publication Date:
2020-01-15T19:02:40Z
AUTHORS (4)
ABSTRACT
During hematogenous metastasis, cancer cells escape from primary lesions and enter into the circulatory system, and only a few can colonize distant organs. However, the mechanism of cell survival and metastasis in the hematopoietic environment remains unclear. Angiorrhea is the character of pathological neovascularization in malignant tumors and commonly detected in osteosarcoma (OS), a bone tumor that prefers circulatory metastasis. In the present study, we focused on the notable role of serum albumin, the highest content in blood plasma, on OS progression. Our results indicated that serum albumin might act as a barrier against exogenous cancer cells during hematogenous metastasis. OS cells with high metastatic potential could gradually obtain strong viability through dedifferentiation under the effect of serum albumin in the angiorrhea region. Further exploration showed that serum albumin could increase the intracellular calcium concentration by activating the voltage-dependent calcium channel Cav2.1 in OS cells to affect the cytoskeleton, sequentially leading to dedifferentiation. Dedifferentiated OS cells with increased FAS apoptosis inhibitory molecule 2 (FAIM2) expression would gradually acquire survival ability, whereas knockdown of FAIM2 caused apoptosis in serum albumin. Moreover, FAIM2 overexpression rescued the viability of OS cells with low metastatic potential in serum albumin. In clinical specimens, OS cells showed markedly stronger positive staining of FAIM2 in the angiorrhea area. Taken together, our findings indicate that serum albumin in the angiorrhea region is a critical substance during pulmonary metastasis of OS cells. Angiorrhea is a nonnegligible prognostic element and FAIM2 might serve as a promising therapeutic target.
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