Science: 150 years of subversion! Harvard scientists have discovered for the first time that lymph nodes are not the only way to metastasize a cancer cell
In 1864, a German doctor Rudolf Virchow surprise when research cancer cells, cancer cells from the original in situ tumor metastasize to distant tissue and lymph nodes (1), at the same time a series of related clinical phenomenon also validate the finding, for example, it was found that some lymph nodes related diseases will significantly promote the transfer of cancer cells (2).
The idea that cancer cells would metastasize over long distances needed to pass through the lymph nodes, which has been popular for more than 150 years.
Until recently, from Massachusetts general hospital cancer institute for biological studies of Kamila Naxerova team led by Dr In the journal science published a super heavy study, to subvert the people for more than 150 years.
Dr Naxerova found in colon cancer patients, only 35% of the patients with the transfer of cancer cells may be done through lymph nodes, and the remaining 65% of the patients, the transfer of cancer cells does not depend on lymph nodes, but directly from the in situ tumor metastasis to other organizations (3).
When it comes to metastatic cancer, you may be familiar.
Cancer cell metastasis is a key indicator that differentiates tumor from benign or malignant, and is also an important factor in predicting survival of patients (4).
In addition, data showed that 90 percent of cancer deaths were caused by metastasis of cancer cells (5).
for example, known as "the king of carcinoma of pancreatic cancer, the 5-year survival rate is only 8%, because more than half of the patients with pancreatic cancer, the cancer had already transferred to other organizations when confirmed, and the 5-year survival rate is only 2.7%, patients and in patients diagnosed with no shift only accounted for 10%, however, the 5 - year survival rate increased significantly, more than 30% (6).
In other words, once cancer cells are transferred to other tissues, the risk of death from pancreatic cancer increases by more than 10 times.
Thus, metastasis is the real killer of cancer.
The classic theory of cancer metastasis, however, as a result of an inevitable corollary is that since the transfer of cancer cells to lymph nodes, so once found the cancer cells in the lymph nodes, by surgical removal of the tumor tissue surrounding lymph nodes can not only limits to the cancer cells continue to transfer, also can reduce the risk of cancer recurrence.
The classic theory of cancer metastasis, however, as a result of an inevitable corollary is that since the transfer of cancer cells to lymph nodes, so once found the cancer cells in the lymph nodes, by surgical removal of the tumor tissue surrounding lymph nodes can not only limits to the cancer cells continue to transfer, also can reduce the risk of cancer recurrence.
Dr Naxerova also wants to determine whether the distal metastasis of cancer cells requires lymph nodes.
Therefore, as early as in 2014, she developed a simple and efficient method, through the analysis of in situ tumor and metastasis after cancer cell genomes china-africa coding region of more than a small piece of guanine (poly real - G) repeat sequence (a sequence to mutations in cancer cell proliferation, and at the same time the sequence mutation also won't affect the normal development of cancer cells and tumor progression), to establish a cancer cell evolutionary tree, to judge the lymph nodes and the origin of cancer cells in distal metastasis tumor tissue (10).
Dr Naxerova idea is very simple, according to the classical view of cancer metastasis and cancer metastasis if passes through the lymph nodes, in lymph node metastases, and then transferred to other organizations (5).
Therefore, the origin of lymph node metastasis and metastatic tumor in distal metastasis should be the same, and should be derived from specific subcellular groups in the in-situ tumor.
That is, the genetic differences between them should be small.
Dr Naxerova idea is very simple, according to the classical view of cancer metastasis and cancer metastasis if passes through the lymph nodes, in lymph node metastases, and then transferred to other organizations (5).
Therefore, the origin of lymph node metastasis and metastatic tumor in distal metastasis should be the same, and should be derived from specific subcellular groups in the in-situ tumor.
That is, the genetic differences between them should be small.
The possible mechanism of metastasis
As a result, the researchers found that in all samples of lymph nodes, 73% of the cancer lymph node is straight out of the in situ tumor and the low correlation with distal metastasis cancer cells and in the same way, all the remote transfer samples, 69% of distal cancerous cells are also derived from in situ tumor directly, and the correlation of lymph node cancer cells is low.
This means that only a small fraction of the cancer cells and the lymphatic metastasis are the same cell subgroups from the tumor tissues.
The lymphatic and distal metastasis of cancer cells in most patients is independent, that is, they arise from different cell subgroups in the primary tumor.
The classic idea of cancer metastasis is not true.
Then, the researchers also analyzed each patients with cancer of the evolutionary tree, found that 35% of patients with distal and the source of the lymph node cancer cells is the same, that is this part of the patient's tumor distal metastasis lymph nodes may be through the complete (it is possible that cancer cells in situ tumor from the distal metastasis happen first, then from the distal metastasis to lymph nodes), and the other 65% of the patients with lymphatic metastasis, and distal metastasis of cancer cells is different from the source, that is to say they are from the different of in situ tumor cells directly transfer out.
The patient's evolutionary tree showed metastatic metastasis from the P4 subgroup in situ to the lymph node (L1) and then metastasized to the distal (red) of the lymph nodes, and N was the normal tissue
All of these results suggest that the metastasis of most cancer cells is not done through the lymph nodes.
As Dr Naxerova said, "we suspect that the lymph node metastasis only shows that the primary tumor is very aggressive and does not lead directly to the formation of distal metastases (11)."
This finding is undoubtedly subversive.
Because the results of this study provides the first evidence for human being, that prevailed in 150 tumor metastasis model does not apply to colon cancer, also means that the value of the lymph nodes were performed with a history of more than 100 years also need to review.
This not only brings guidance to clinical treatment, but also facilitates the further study of cancer cell transfer mechanism.
If one day the metastasis of the cancer cells could be suppressed, then the cancer would become a paper tiger.
Reference:
1.Virchow R. Die krankhaften Geschwülste; dreissig Vorlesungen: gehalten während des Wintersemesters 1862-1863 an der Universität zu Berlin[M]. Hirschwald, 1864.
2.Halsted W S. Results of radical operation for the cure of carcinoma of breast[J]. Ann surg, 1907, 46: 1-19.
3.Naxerova K, Reiter J G, Brachtel E, et al. Origins of lymphatic and distant metastases in human colorectal cancer[J]. Science, 2017, 357(6346): 55-60.
4.Nathanson S D. Insights into the mechanisms of lymph node metastasis[J]. Cancer, 2003, 98(2): 413-423.
5.Chaffer C L, Weinberg R A. A perspective on cancer cell metastasis[J]. Science, 2011, 331(6024): 1559-1564.
6.https://seer.cancer.gov/statfacts/html/pancreas.html
7.Moynihan B G A. The surgical treatment of cancer of the sigmoid flexure and rectum[J]. Surg Gynaecol Obstet, 1908, 6: 463.
8.Gervasoni Jr J E, Sbayi S, Cady B. Role of lymphadenectomy in surgical treatment of solid tumors: an update on the clinical data[J]. Annals of surgical oncology, 2007, 14(9): 2443-2462.
9.Faries M B, Thompson J F, Cochran A J, et al. Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma[J]. New England Journal of Medicine, 2017, 376(23): 2211-2222.
10.Naxerova K, Brachtel E, Salk J J, et al. Hypermutable DNA chronicles the evolution of human colon cancer[J]. Proceedings of the National Academy of Sciences, 2014, 111(18): E1889-E1898.
11.http://www.ajmc.com/newsroom/new-isciencei-paper-questions-sequential-role-of-lymph-nodes-in-crc-metastases