109 research outputs found
Π‘Π ΠΠΠΠΠ’ΠΠΠ¬ΠΠ«Π ΠΠΠΠΠΠ ΠΠΠΠΠ‘ΠΠ ΠΠΠΠ’ΠΠ ΠΠ‘Π’Π ΠΠΠΠ-Π ΠΠΠΠ‘Π’ΠΠΠ’ΠΠΠΠ Π ΠΠΠ ΠΠΠΠΠ§ΠΠΠ ΠΠΠΠΠΠ«
The exosomes involvement in the pathogenesis of tumors is based on their property to incorporate into theΒ recipient cells resulting in the both genomic and epigenomic changes.Β Earlier we have shown that exosomesΒ from different types of estrogen-independent breastΒ cancer cells (MCF-7/T developed by long-term tamoxifenΒ treatment, and MCF-7/M)Β developed by metformin treatment were able to transfer resistance to the parentΒ MCF-7Β cells. To elucidate the common features of the both types of resistant exosomes, theΒ proteome andΒ microRNA cargo of the control and both types of the resistant exosomes wereΒ analyzed. Totally, more thanΒ 400 proteins were identified in the exosome samples. Of theseΒ proteins, only two proteins, DMBT1 (Deleted inΒ Malignant Brain Tumors 1) and THBS1Β (Thrombospondin-1), were commonly expressed in the both resistantΒ exosomes (less thanΒ 5% from total DEPs) demonstrating the unique protein composition of each type of theΒ resistant exosomes. The comparative analysis of the miRNA differentially expressed inΒ the both MCF-7/T andΒ MCF-7/M resistant exosomes revealed 180 up-regulated and 202Β down-regulated miRNAs. Among them,Β 4 up-regulated and 8 down-regulated miRNAs wereΒ associated with progression of hormonal resistance ofΒ breast tumors. The bioinformaticalΒ analysis of 4 up-regulated exosomal miRNAs revealed 2 miRNAs, mir-Β 101and mir-181b, which up-regulated PI3K signalingΒ supporting the key role of PI3K/Akt in the developmentΒ of the resistant phenotype of breast cancer cells.Π£ΡΠ°ΡΡΠΈΠ΅ ΡΠΊΠ·ΠΎΡΠΎΠΌ Π² ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π΅ Π·Π»ΠΎΠΊΠ°ΡΠ΅ΡΡΠ²Π΅Π½Π½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΎ Π½Π° ΠΈΡ
ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΏΡΠΎΠ½ΠΈΠΊΠ°ΡΡ Π²Π½ΡΡΡΡΒ ΠΊΠ»Π΅ΡΠΎΠΊ-ΡΠ΅ΡΠΈΠΏΠΈΠ΅Π½ΡΠΎΠ², Π²ΡΠ·ΡΠ²Π°Ρ Π² ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΡ
ΠΊΠ°ΡΠΊΠ°Π΄ Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈ ΡΠΏΠΈΠ³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ. Π Π°Π½Π΅Π΅Β ΠΌΡΒ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΡΠΊΠ·ΠΎΡΠΎΠΌΡ, ΠΏΡΠΎΠ΄ΡΡΠΈΡΡΠ΅ΠΌΡΠ΅ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ Π²Π°ΡΠΈΠ°Π½ΡΠ°ΠΌΠΈ ΡΡΡΡΠΎΠ³Π΅Π½-Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΡ
ΡΡΠ±Π»ΠΈΠ½ΠΈΠΉΒ ΠΊΠ»Π΅ΡΠΎΠΊΒ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ (MCF-7/T, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠΉ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ³ΠΎ ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊΒ Π²Β ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ Π°Π½ΡΠΈΡΡΡΡΠΎΠ³Π΅Π½Π° ΡΠ°ΠΌΠΎΠΊΡΠΈΡΠ΅Π½Π°, ΠΈ MCF-7/M, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠΉ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΠΊΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΡΒ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΒ ΠΌΠ΅ΡΡΠΎΡΠΌΠΈΠ½ΠΎΠΌ), ΡΠΏΠΎΡΠΎΠ±Π½Ρ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡ Π² ΡΠΎΠ΄ΠΈΡΠ΅Π»ΡΡΠΊΠΈΡ
ΠΊΠ»Π΅ΡΠΊΠ°Ρ
MCF-7.Β Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΠ΅Β Π΄Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠ½ΡΡ
ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠ΅ΠΉ ΡΠΎΡΡΠ°Π²Π° ΡΠΊΠ·ΠΎΡΠΎΠΌ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
Β ΠΊΠ»Π΅ΡΠΎΠΊ Π±ΡΠ» ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½Β ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ° ΠΈ ΠΏΡΠΎΡΠΈΠ»Ρ ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½ΡΡ
ΡΠΊΠ·ΠΎΡΠΎΠΌ ΠΈΒ ΡΠΊΠ·ΠΎΡΠΎΠΌ, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ
ΠΎΡΒ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΡΡΠ±Π»ΠΈΠ½ΠΈΠΉ. Π ΡΠ΅Π»ΠΎΠΌ Π² ΠΎΠ±ΡΠ°Π·ΡΠ°Ρ
ΡΠΊΠ·ΠΎΡΠΎΠΌ Π±ΡΠ»ΠΎ ΠΈΠ΄Π΅Π½ΡΠΈΡΠΈΡΠΈΡΠΎΠ²Π°Π½ΠΎΒ Π±ΠΎΠ»Π΅Π΅ 400 Π±Π΅Π»ΠΊΠΎΠ², ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ
Β ΡΠΎΠ»ΡΠΊΠΎ 2 Π±Π΅Π»ΠΊΠ°, DMBT1 (Deleted in Malignant Brain Tumors 1) ΠΈ THBS1Β (Thrombospondin-1), Π±ΡΠ»ΠΈΒ Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Ρ Π² ΠΎΠ±ΠΎΠΈΡ
ΡΠΈΠΏΠ°Ρ
ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΡΠΊΠ·ΠΎΡΠΎΠΌ (ΠΌΠ΅Π½Π΅Π΅ 5 % ΠΎΡΒ ΠΎΠ±ΡΠ΅Π³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° Π±Π΅Π»ΠΊΠΎΠ²,Β Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π² ΡΠΊΠ·ΠΎΡΠΎΠΌΠ°Ρ
ΡΠ΅Π·ΠΈΡΡΠ΅ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ), ΡΡΠΎΒ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎΠ± ΡΠ½ΠΈΠΊΠ°Π»ΡΠ½ΠΎΠΌΒ ΡΠΎΡΡΠ°Π²Π΅ ΡΠΊΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΡΡ
Π±Π΅Π»ΠΊΠΎΠ² Π΄Π»Ρ ΠΊΠ°ΠΆΠ΄ΠΎΠ³ΠΎ ΡΠΈΠΏΠ° ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ.Β Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ·Β ΡΠΎΡΡΠ°Π²Π° ΠΌΠΈΠΊΡΠΎΠ ΠΠ, Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Π² ΠΎΠ±ΠΎΠΈΡ
Π²Π°ΡΠΈΠ°Π½ΡΠ°Ρ
Β ΡΠΊΠ·ΠΎΡΠΎΠΌ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ,Β Π²ΡΡΠ²ΠΈΠ» 180 Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ ΠΈ 202 ΠΌΠΈΠΊΡΠΎΠ ΠΠ Ρ ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½Π½ΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠ΅ΠΉ. Π‘ΡΠ΅Π΄ΠΈ Π½ΠΈΡ
4Β Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΈ 8 Π³ΠΈΠΏΠΎΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠΒ ΠΎΠΊΠ°Π·Π°Π»ΠΈΡΡ Π°ΡΡΠΎΡΠΈΠΈΡΠΎΠ²Π°Π½Ρ Ρ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ΠΌΒ Π³ΠΎΡΠΌΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ.Β ΠΠΈΠΎΠΈΠ½ΡΠΎΡΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· 4Β Π³ΠΈΠΏΠ΅ΡΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΌΠΈΠΊΡΠΎΠ ΠΠ Π²ΡΡΠ²ΠΈΠ» 2 ΠΌΠΈΠΊΡΠΎΠ ΠΠ, mir-101ΠΈΒ mir-181b, ΡΡΠ°ΡΡΠ²ΡΡΡΠΈΡ
Π² ΡΡΠΈΠΌΡΠ»ΡΡΠΈΠΈ PI3KΒ ΡΠΈΠ³Π½Π°Π»ΠΈΠ½Π³Π°, ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΡ ΠΎ Π²Π°ΠΆΠ½ΠΎΠΉ ΡΠΎΠ»ΠΈ ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅Π³ΠΎ Π²Β ΡΠ°Π·Π²ΠΈΡΠΈΠΈ Π³ΠΎΡΠΌΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈΒ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ.
ΠΠΊΠ·ΠΎΡΠΎΠΌΡ ΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΊ ΠΌΠ΅ΡΡΠΎΡΠΌΠΈΠ½Ρ: ΠΏΠΈΠ»ΠΎΡΠ½ΠΎΠ΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅
Objective: to study the role of the intercellular interactions in the progression of the cancer cells resistance to metformin, a biguanide antidiabetic drug exhibited the marked anti-tumor activity.Results. Earlier we have demonstrated the effect of horizontal transferring of hormonal resistance of breast cancer cellsΒ from cell to cell, and showed the key role of exosomes on the transferring of the resistance. Here we have shown the effect of the horizontal transferring of metformin resistance in breast cancer cells β similar to the progression of hormonal resistance. We found that horizontal transferring of the metformin resistance is mediated via exosomes secreted by the resistant cells. The proteome analysis of the exosomes revealed several proteins differentially expressed in the exosomes of metformin-resistant cells and associated with the regulation of cell response to apoptotic drugs.Conclusions. Totally, the data presented demonstrate the new mechanism of the development of the cancer cell resistance based on the intercellular interactions, opening the new insights in the target therapy of breast cancer.Π¦Π΅Π»Ρ ΡΠ°Π±ΠΎΡΡ β ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ ΠΌΠ΅ΠΆΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΠΉ Π² ΡΠ°Π·Π²ΠΈΡΠΈΠΈ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΊ ΠΌΠ΅ΡΡΠΎΡΠΌΠΈΠ½Ρ β Π°Π½ΡΠΈΠ΄ΠΈΠ°Π±Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΌΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΠΈΠ· Π³ΡΡΠΏΠΏΡ Π±ΠΈΠ³ΡΠ°Π½ΠΈΠ΄ΠΎΠ², ΠΎΠ±Π»Π°Π΄Π°ΡΡΠ΅ΠΌΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΌ ΡΡΡΠ΅ΠΊΡΠΎΠΌ.Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. Π ΠΎΡΠ½ΠΎΠ²Ρ ΡΠ°Π±ΠΎΡΡ Π»Π΅Π³Π»ΠΈ Π΄Π°Π½Π½ΡΠ΅, ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π½Π°ΠΌΠΈ ΡΠ°Π½Π΅Π΅ ΠΏΡΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ Π³ΠΎΡΠΌΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΠΊΠ»Π΅ΡΠΎΠΊ ΡΠ°ΠΊΠ° ΠΌΠΎΠ»ΠΎΡΠ½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ ΠΈ ΠΏΡΠΎΠ΄Π΅ΠΌΠΎΠ½ΡΡΡΠΈΡΠΎΠ²Π°Π²ΡΠΈΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠΈ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΠ³ΠΎ ΡΠ΅Π½ΠΎΡΠΈΠΏΠ° Π³ΠΎΡΠΈΠ·ΠΎΠ½ΡΠ°Π»ΡΠ½ΡΠΌ ΠΏΡΡΠ΅ΠΌ, ΠΎΡ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΊ ΠΊΠ»Π΅ΡΠΊΠ΅, Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Ρ ΡΡΠ°ΡΡΠΈΠ΅ΠΌ ΡΠΊΠ·ΠΎΡΠΎΠΌ. Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΌΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΡΡΠΎΠΉΡΠΈΠ²ΠΎΡΡΠΈ ΠΊ ΠΌΠ΅ΡΡΠΎΡΠΌΠΈΠ½Ρ Π³ΠΎΡΠΈΠ·ΠΎΠ½ΡΠ°Π»ΡΠ½ΡΠΌ ΠΏΡΡΠ΅ΠΌ, ΠΊΠ°ΠΊ ΠΈ Π² ΡΠ»ΡΡΠ°Π΅ Π³ΠΎΡΠΌΠΎΠ½Π°Π»ΡΠ½ΠΎΠΉ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΠ΅ΡΠ°ΡΡΠΈΠΌ ΡΠ°ΠΊΡΠΎΡΠΎΠΌ Π² ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΌ Π³ΠΎΡΠΈΠ·ΠΎΠ½ΡΠ°Π»ΡΠ½ΠΎΠΌ ΠΏΡΡΠΈ ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠΈ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ ΡΠ²Π»ΡΡΡΡΡ ΠΌΠ΅ΠΆΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ, ΡΠ΅Π°Π»ΠΈΠ·ΡΠ΅ΠΌΡΠ΅ Π² ΡΠΎΠΌ ΡΠΈΡΠ»Π΅ Ρ ΡΡΠ°ΡΡΠΈΠ΅ΠΌ ΡΠΊΠ·ΠΎΡΠΎΠΌ, ΠΏΡΠΎΠ΄ΡΡΠΈΡΡΠ΅ΠΌΡΡ
ΠΌΠ΅ΡΡΠΎΡΠΌΠΈΠ½ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΠΌΠΈ ΠΊΠ»Π΅ΡΠΊΠ°ΠΌΠΈ. ΠΠ½Π°Π»ΠΈΠ· ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ° ΡΠΊΠ·ΠΎΡΠΎΠΌ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠ΄ΠΈΠ» ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠ΅ Π² ΡΠΊΠ·ΠΎΡΠΎΠΌΠ°Ρ
ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΊΠ»Π΅ΡΠΎΠΊ Π±Π΅Π»ΠΊΠΎΠ², ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΡΠΈΡ
ΠΎΡΠ²Π΅Ρ ΠΊΠ»Π΅ΡΠΎΠΊ Π½Π° Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ Π°ΠΏΠΎΠΏΡΠΎΡΠΈΡΠ΅ΡΠΊΠΈΡ
Π°Π³Π΅Π½ΡΠΎΠ².ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠΎΠ»ΡΡΠ΅Π½Π½ΡΠ΅ Π΄Π°Π½Π½ΡΠ΅ ΠΏΠΎΠ΄ΡΠ²Π΅ΡΠΆΠ΄Π°ΡΡ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ Π½Π΅ΠΈΠ·Π²Π΅ΡΡΠ½ΠΎΠ³ΠΎ ΡΠ°Π½Π΅Π΅ ΠΌΠ΅Ρ
Π°Π½ΠΈΠ·ΠΌΠ° ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½ΠΈΡ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΠΈ, ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π½Π° ΠΌΠ΅ΠΆΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ
Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡΡ
, ΠΈ ΠΎΡΠΊΡΡΠ²Π°ΡΡ Π½ΠΎΠ²ΡΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΠΈ Π² ΠΏΠΎΠΈΡΠΊΠ΅ ΠΌΠΈΡΠ΅Π½Π΅ΠΉ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ
Traumatic-event headaches
BACKGROUND: Chronic headaches from head trauma and whiplash injury are well-known and common, but chronic headaches from other sorts of physical traumas are not recognized. METHODS: Specific information was obtained from the medical records of 15 consecutive patients with chronic headaches related to physically injurious traumatic events that did not include either head trauma or whiplash injury. The events and the physical injuries produced by them were noted. The headaches' development, characteristics, duration, frequency, and accompaniments were recorded, as were the patients' use of pain-alleviative drugs. From this latter information, the headaches were classified by the diagnostic criteria of the International Headache Society as though they were naturally-occurring headaches. The presence of other post-traumatic symptoms and litigation were also recorded. RESULTS: The intervals between the events and the onset of the headaches resembled those between head traumas or whiplash injuries and their subsequent headaches. The headaches themselves were, as a group, similar to those after head trauma and whiplash injury. Thirteen of the patients had chronic tension-type headache, two had migraine. The sustained bodily injuries were trivial or unidentifiable in nine patients. Fabrication of symptoms for financial remuneration was not evident in these patients of whom seven were not even seeking payments of any kind. CONCLUSIONS: This study suggests that these hitherto unrecognized post-traumatic headaches constitute a class of headaches characterized by a relation to traumatic events affecting the body but not including head or whiplash traumas. The bodily injuries per se can be discounted as the cause of the headaches. So can fabrication of symptoms for financial remuneration. Altered mental states, not systematically evaluated here, were a possible cause of the headaches. The overall resemblance of these headaches to the headaches after head or whiplash traumas implies that these latter two headache types may likewise not be products of structural injuries
COMPARATIVE ANALYSIS OF THE EXOSOMAL CARGO OF THE ESTROGEN-RESISTANT BREAST CANCER CELLS
The exosomes involvement in the pathogenesis of tumors is based on their property to incorporate into theΒ recipient cells resulting in the both genomic and epigenomic changes.Β Earlier we have shown that exosomesΒ from different types of estrogen-independent breastΒ cancer cells (MCF-7/T developed by long-term tamoxifenΒ treatment, and MCF-7/M)Β developed by metformin treatment were able to transfer resistance to the parentΒ MCF-7Β cells. To elucidate the common features of the both types of resistant exosomes, theΒ proteome andΒ microRNA cargo of the control and both types of the resistant exosomes wereΒ analyzed. Totally, more thanΒ 400 proteins were identified in the exosome samples. Of theseΒ proteins, only two proteins, DMBT1 (Deleted inΒ Malignant Brain Tumors 1) and THBS1Β (Thrombospondin-1), were commonly expressed in the both resistantΒ exosomes (less thanΒ 5% from total DEPs) demonstrating the unique protein composition of each type of theΒ resistant exosomes. The comparative analysis of the miRNA differentially expressed inΒ the both MCF-7/T andΒ MCF-7/M resistant exosomes revealed 180 up-regulated and 202Β down-regulated miRNAs. Among them,Β 4 up-regulated and 8 down-regulated miRNAs wereΒ associated with progression of hormonal resistance ofΒ breast tumors. The bioinformaticalΒ analysis of 4 up-regulated exosomal miRNAs revealed 2 miRNAs, mir-Β 101and mir-181b, which up-regulated PI3K signalingΒ supporting the key role of PI3K/Akt in the developmentΒ of the resistant phenotype of breast cancer cells
Combined treatment of human multiple myeloma cells with bortezomib and doxorubicin alters the interactome of 20S proteasomes
Exosomes and development of cancer cell resistance to metformin: pilot study
Objective: to study the role of the intercellular interactions in the progression of the cancer cells resistance to metformin, a biguanide antidiabetic drug exhibited the marked anti-tumor activity.Results. Earlier we have demonstrated the effect of horizontal transferring of hormonal resistance of breast cancer cellsΒ from cell to cell, and showed the key role of exosomes on the transferring of the resistance. Here we have shown the effect of the horizontal transferring of metformin resistance in breast cancer cells β similar to the progression of hormonal resistance. We found that horizontal transferring of the metformin resistance is mediated via exosomes secreted by the resistant cells. The proteome analysis of the exosomes revealed several proteins differentially expressed in the exosomes of metformin-resistant cells and associated with the regulation of cell response to apoptotic drugs.Conclusions. Totally, the data presented demonstrate the new mechanism of the development of the cancer cell resistance based on the intercellular interactions, opening the new insights in the target therapy of breast cancer
p53 Affects Zeb1 Interactome of Breast Cancer Stem Cells
P53 is a critical tumor suppressor that protects the integrity of genome and prevents cells from malignant transformation, including metastases. One of the driving forces behind the onset of metastases is the epithelial to mesenchymal transition (EMT) program. Zeb1 is one of the key transcription factors that govern EMT (TF-EMT). Therefore, the interaction and mutual influence of p53 and Zeb1 plays a critical role in carcinogenesis. Another important feature of tumors is their heterogeneity mediated by the presence of so-called cancer stem cells (CSCs). To this end, we have developed a novel fluorescent reporter-based approach to enrich the population of CSCs in MCF7 cells with inducible expression of Zeb1. Using these engineered cell lines, we studied the effect of p53 on Zeb1 interactomes isolated from both CSCs and regular cancer cells. By employing co-immunoprecipitations followed by mass spectrometry, we found that the composition of Zeb1 interactome was affected not only by the p53 status but also by the level of Oct4/Sox2 expression, indicating that stemness likely affects the specificity of Zeb1 interactions. This study, together with other proteomic studies of TF-EMT interactomes, provides a framework for future molecular analyses of biological functions of Zeb1 at all stages of oncogenesis
[Mass-spectrometric analysis of proteasomal subunits possessing endoribonuclease activity]
Proteasomes act as the main apparatus of non-lysosomal intracellular proteolysis and participate in the regulation of most important cellular processes. Despite considerable progress in the understanding of proteasome's functioning, some issues, in particular, RNase activity of these ribonucleoprotein complexes and its regulation remain scarcely explored. In this paper we found several proteins corresponding by electrophoretic mobility to subunits of the complex 20S proteasome to possess endoribonuclease activity with respect to both sense and antisense sequences of the c-myc mRNA 3'-UTR. Mass-spectrometric analysis of tryptic hydrolysates of these proteins revealed in the samples the presence of 20S proteasome subunits--Ξ±l (PSMA6), Ξ±5 (PSMA5), Ξ±6 (PSMA1) and Ξ±7 (PSMA3). A number of novel phosphorylation sites in subunits Ξ±l (PSMA6) and Ξ±7 (PSMA3), and the form of subunit Ξ±5 (PSMA5) with a deletion of N-terminal 20 amino acid residues detected. The observed differences of individual subunits in the possession endonuclease activity could be apparently explained by postranslational modifications of these proteins, in particular--by phosphorylation. It is shown that the specificity of the proteasomal RNase activity varies after dephosphorylation and also influenced by Ca and Mg cations. The conclusions made about the impact of the PTM status of proteasome subunits on the specificity of their RNase activity
Proteomic Profiling of the Human Fetal Multipotent Mesenchymal Stromal Cells Secretome
Secretome of multipotent mesenchymal stromal cells (MSCs) is actively used in biomedical applications such as alveolar bone regeneration, treatment of cardiovascular disease, and neurodegenerative disorders. Nevertheless, hMSCs have low proliferative potential and production of the industrial quantity of their secretome might be challenging. Human fetal multipotent mesenchymal stromal cells (FetMSCs) isolated from early human embryo bone marrow are easy to expand and might be a potential source for pharmaceutical substances production based on their secretome. However, the secretome of FetMSCs was not previously analyzed. Here, we describe the secretome of FetMSCs using LC-MALDI shotgun proteomics. We identified 236 proteins. Functional annotation of the identified proteins revealed their involvement in angiogenesis, ossification, regulation of apoptosis, and immune response processes, which made it promising for biomedical applications. The proteins identified in the FetMSCs secretome are involved in the same biological processes as proteins from previously described adult hMSCs secretomes. Nevertheless, many of the common hMSCs secretome components (such as VEGF, FGF, Wnt and TGF-β) have not been identified in the FetMSCs secretome
New putative phenol oxidase in ascidian blood cells
The phenol oxidase system is ancient and ubiquitously distributed in all living organisms. In various groups it serves for the biosynthesis of pigments and neurotransmitters (dopamine), defence reactions and tissue hardening. Ascidians belong to subphylum Tunicata, which is considered the closest living relative to Vertebrates. Two phenol oxidases previously described for ascidians are vertebrate-like and arthropod-like phenol oxidases. In our present study, we described a new ascidian protein, Tuphoxin, with putative phenol oxidase function, which bears no sequence similarity with two enzymes described previously. The closest related proteins to Tuphoxin are mollusc haemocyanins. Unlike haemocyanins, which are oxygen transporting plasma proteins, Tuphoxin is synthesised in ascidian blood cells and secreted in the extracellular matrix of the tunicβascidian outer coverings. Single mature transcript coding for this phenol oxidase can give several protein products of different sizes. Thus limited proteolysis of the initial protein is suggested. A unique feature of Tuphoxins and their homologues among Tunicata is the presence of thrombospondin first type repeats (TSP1) domain in their sequence which is supposed to provide interaction with extracellular matrix. The finding of TSP1 in the structure of phenol oxidases is new and we consider this to be an innovation of Tunicata evolutionary lineage
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